B-cell-mediated antibody responses are essential for eliminating invading pathogens. BCRs expressed on the B-cell surface detect the presence of cognate antigens. The binding of antigens to the BCR leads to the activation of signaling cascades (Reth and Wienands, 1997; Dal Porto et al., 2004; Kwak et al., 2019), which induce transcriptional programs that prepare B-cells for proliferation and differentiation (Kurosaki et al., 2010; Shlomchik et al., 2019; Wang et al., 2020). BCR signaling also induces rapid antigen internalization, processing, and presentation for T-cell recognition, which provides the second signal required for B-cell clonal expansion and differentiation to high-affinity antibody-secreting cells and memory B-cells (Song et al., 1995; Gitlin et al., 2014). BCR signaling is tightly regulated by various external and internal factors to activate antibody responses that are specific and also qualitatively and quantitatively matched to the encountered antigen.

Antigen-induced receptor reorganization activates BCRs at the B-cell surface. Antigen binding leads to BCR clustering at lipid rafts, which enables raft-resident kinases, such as the Src kinases Lyn and Fyn, to phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic domains of the BCR signaling subunit CD79a/b heterodimer (Reth, 1994; Pierce, 2002; Sohn et al., 2008). Doubly phosphorylated ITAMs recruit and activate spleen tyrosine kinase (Syk), which in turn activates multiple downstream signaling pathways, including phospholipase Cγ2 (PLCγ2), Bruton’s tyrosine kinase (Btk), Ras-GTPase, and phosphatidylinositol-3 kinase (PI3K), initiating signaling cascades (Kurosaki, 2000; Dal Porto et al., 2004; Tanaka and Baba, 2020). Signaling activation also induces the recruitment and activation of inhibitory phosphatases, such as SH2-containing tyrosine phosphatase-1 (SHP-1) and phosphatidylinositol-5 phosphatase-1 (SHIP-1), to BCR signaling complexes (Brauweiler et al., 2000; Gross et al., 2009; Franks and Cambier, 2018). SHIP-1 and SHP-1 negatively regulate BCR signaling by inactivating the plasma membrane docking lipids for stimulatory kinases, such as Btk and Akt (Aman et al., 1998; Bolland et al., 1998) and dephosphorylating the BCR and its downstream signaling molecules (Mizuno et al., 2000; Adachi et al., 2001), respectively. The interplay between the stimulatory kinases and the inhibitory phosphatases controls the balance of antibody responses against pathogens and self. Deficiencies in stimulatory kinases by mutations, such as Btk, cause X-linked agammaglobulinemia (XLA) (Kinnon et al., 1993), while deficiencies in the inhibitory phosphatases SHP-1 or SHIP-1 result in autoimmune diseases (Pao et al., 2007; Leung et al., 2013). However, the mechanisms by which BCR signaling attenuation is initiated and regulated remain elusive.

B-cells encounter both soluble and membrane-associated antigens in vivo. Membrane-associated antigens include antigens on antigen-presenting cells, like follicular dendritic cells in B-cell follicles or germinal centers, and pathogenic cells, like bacteria, parasites, and cancer cells (Batista and Harwood, 2009; Depoil et al., 2009; Gonzalez et al., 2009; Cyster, 2010). The binding of multi-valent soluble antigen and membrane-associated antigen with any valency induces dynamic reorganization of surface BCRs into microclusters, triggering BCR signaling. Subsequently, surface BCRs continue moving to the plasma membrane region contacting antigen-presenting surfaces or to one B-cell pole in the case of soluble antigen, which leads to the growth and merger of BCR microclusters and the formation of immunological synapses (Carrasco et al., 2004; Harwood and Batista, 2010) or supra-molecular activation complexes (Unanue and Karnovsky, 1973; Schreiner and Unanue, 1977; Tolar et al., 2009b; Harwood and Batista, 2010).

Multiple mechanisms have been proposed for signaling initiation by antigen-induced surface BCR reorganization. The binding of surface BCRs to membrane-associated antigen has been shown to induce a conformational change in the BCR extracellular domain, exposing a proximal membrane region of membrane IgM that promotes receptor clustering (Tolar et al., 2009a; Shen et al., 2019). Antigen-binding also changes the conformation of the BCR cytoplasmic domains from a closed to an open form, facilitating the recruitment of signaling molecules (Tolar et al., 2005). Alternatively, antigen-BCR interaction can increase the molecular spacing of BCRs in clusters, facilitating BCR interaction with signaling molecules (Yang and Reth, 2010; Kläsener et al., 2014). The inhibitory phosphatases SHP-1 and SHIP-1 are also recruited to BCR clusters (Adachi et al., 2001; Seeley-Fallen et al., 2014). However, the mechanisms underlying phosphatase recruitment and its relationship with BCR signaling activation complexes are unknown.

The actin cytoskeleton is essential for antigen-induced BCR reorganization on the B-cell surface in response to both soluble and membrane-associated antigen (Harwood and Batista, 2011; Liu et al., 2013b; Song et al., 2013; Hoogeboom and Tolar, 2016). Early signaling of the BCR triggers transient actin depolymerization via Rap GTPase and its downstream target cofilin (Freeman et al., 2011), which disassembles the existing cortical actin network that confines the lateral movement of surface BCRs (Treanor et al., 2010). Following this transient depolymerization, BCR signaling activates rapid actin polymerization through the actin nucleation-promoting factors Wiskott-Aldrich Syndrome Protein (WASP) and neuronal-WASP (N-WASP), modulating BCR mobility and leading to F-actin accumulation at BCR-antigen interaction sites (Liu et al., 2013a; Rey-Suarez et al., 2020). Actin polymerization and treadmilling in B-cells stimulated by soluble antigens drive surface BCRs to cluster and move to one pole of the B-cell, forming a BCR cap (Schreiner and Unanue, 1977; Liu et al., 2012a). Upon interacting with membrane-associated antigens, B-cells organize actin into two dynamic structures. One treadmills outwards, driving B-cell membrane spreading and expanding the B-cell membrane region contacting the antigen-presenting surface (contact zone), which enables more BCRs to engage antigen (Bolger-Munro et al., 2019). The other creates retrograde flow towards the center of the B-cell contact zone, driving the centripetal movement and growth of BCR microclusters (Liu et al., 2012b). Together, these processes amplify BCR signaling (Batista et al., 2010; Harwood and Batista, 2011). The extent of B-cell spreading and the amount of BCR-antigen complexes gathered in the contact zone depend on BCR binding affinity and the density of antigen on the membrane (Fleire et al., 2006). Subsequent to spreading, B-cells contract, reducing the contact area, which drives BCR microclusters to merge into central clusters to form immunological synapses (Fleire et al., 2006; Liu et al., 2013a).

The actin cytoskeleton closely interplays with BCR signaling. We have previously shown that mouse primary B-cells with Btk deficiency (Liu et al., 2011) or double knockouts of the actin nucleation-promoting factors WASP and N-WASP (Liu et al., 2013a) fail to spread on antigen-presenting surfaces and establish stable interactions with membrane-associated antigen, drastically reducing BCR signaling. Btk can activate WASP and N-WASP through Vav, the guanine nucleotide exchange factor of Cdc42 and Rac, and phosphatidylinositol-5 kinase that generates phosphatidylinositol-4,5-biphosphate (PI4,5P₂) (Sharma et al., 2009; Padrick and Rosen, 2010). Surprisingly, B-cell-specific knockout of N-WASP (cNKO) but not Wasp germline knockout (WKO) enhances B-cell spreading, delays B-cell contraction, and inhibits the centralization of BCR clusters at the contact zone (Liu et al., 2013a). Consistent with these findings, Bolger-Munro et al. have shown that knockdown of the actin nucleation factor Arp2/3 downstream of WASP and N-WASP disrupts the dynamic actin reorganization induced by membrane-associated antigen required for BCR microcluster growth and merger (Bolger-Munro et al., 2019). Using B-cell-specific and germline knockouts, we showed that in addition to N-WASP, the actin motor non-muscle myosin IIA (NMIIA) (Seeley-Fallen et al., 2022) and the actin-binding adaptor protein Abp1 (Seeley-Fallen et al., 2014) are required for B-cell contraction and BCR central cluster formation. Finally, Wang et al., 2022 recently showed that in the presence of the adhesion molecule ICAM on the antigen-presenting surface, B-cells form contractile actomyosin arcs, driving centripetal movement of BCR clusters in the B-cell contact zone. Together, these findings indicate a critical role of different actin networks in B-cell contraction and BCR signaling.

Our previous studies demonstrate that B-cell contraction is critical for BCR signaling attenuation. Delay or inhibition of B-cell contraction due to deficiencies in actin regulators, N-WASP, Abp1, or NMIIA, prolongs and/or increases BCR signaling by enhancing the activation of stimulatory kinases and suppressing the activation of inhibitory phosphatases, which elevates the production of autoantibody levels in mice (Liu et al., 2013a; Seeley-Fallen et al., 2014; Seeley-Fallen et al., 2022). N-WASP and NMIIA are not known to interact with kinases and phosphatases directly. The growth, merger, and centralization of antigen-BCR complexes at the B-cell contact zone during the B-cell contraction phase are associated with reduced BCR signaling capability (Liu et al., 2013a). These findings suggest that B-cell contraction is one of the mechanisms for inducing BCR signaling attenuation. However, how the actin cytoskeleton facilitates the transition of the spreading to the contraction phase and how B-cell contraction switches BCR signaling from amplification to attenuation is unknown.

This study explores the mechanisms by which the actin cytoskeleton remodels from spreading lamellipodia to contractile structures and by which B-cell contraction suppresses BCR signaling. Our results show that the contractile actomyosin structures responsible for B-cell contraction originate from branched actin at spreading lamellipodia. N-WASP/Arp2/3-mediated actin polymerization prolongs the lifetime of the lamellipodial actin structures, enables NMIIA recruitment, and drives their movement to the center of the B-cell contact zone. B-cell contraction increases the molecular density within individual BCR-antigen clusters, which promotes the disassociation of both the stimulatory kinase Syk and the inhibitory phosphatases SHIP-1 from BCR clusters, leading to signal attenuation. Our study reveals a new mechanism underlying BCR signal downregulation.

When binding membrane-associated antigens, naive follicular B-cells undergo actin-mediated spreading followed by a contraction, which amplifies BCR signaling and promotes immunological synapse formation (Fleire et al., 2006; Harwood and Batista, 2011). We previously showed that B-cell contraction after spreading on antigen-presenting surfaces promotes BCR signaling attenuation (Liu et al., 2013a; Seeley-Fallen et al., 2022). However, how the actin cytoskeleton reorganizes as B-cells transition from spreading to contraction and how B-cell contraction downregulates BCR signaling have been elusive. Here, we demonstrate that inner F-actin foci formed at the contact zone distal to the lamellipodial F-actin network promote B-cells to switch from spreading to contraction. These inner foci are derived from the lamellipodial F-actin network that mediates spreading, are generated by N-WASP- but not WASP-activated Arp2/3-mediated branched actin polymerization, and facilitate NMII recruitment. N-WASP-activated actin polymerization coordinates with NMII to form actomyosin ring-like structures, enabling B-cell contraction. B-cell contraction increases BCR molecular density in existing clusters, which promotes the disassociation of both the stimulatory kinase Syk and the inhibitory phosphatase SHIP-1, leading to signaling attenuation.

One significant finding of this study is that Arp2/3-mediated polymerization of branched actin is required for B-cell contraction. Arp2/3-mediated branched actin polymerization is known to drive B-cell spreading and to create actin centripetal flow at the contact zone between B-cells and antigen-presenting surface (Bolger-Munro et al., 2019). The actin structure that supports B- and T-cell spreading to form the immunological synapse with antigen-presenting cells is similar to lamellipodial F-actin networks found in adherent cells (Bunnell et al., 2001; Koestler et al., 2008; Bolger-Munro et al., 2019). Lamellipodial F-actin networks consist primarily of branched actin filaments polymerizing against the plasma membrane interspersed with bundled actin filaments (Krause and Gautreau, 2014; Skau and Waterman, 2015). Contractile actin structures, such as stress fibers, are typically generated from bundled actin filaments, as observed in adherent and migrating cells (Levayer and Lecuit, 2012; Tojkander et al., 2015; Hammer et al., 2019). Here, we show that inner F-actin foci, generated by Arp2/3-mediated actin polymerization, transition B-cells from spreading to contraction. Furthermore, these inner F-actin foci are directly derived from lamellipodial F-actin networks. Based on the observed dynamics, we infer that instead of polymerizing against the plasma membrane, Arp2/3 appears to nucleate actin polymerization in the opposite direction, sustaining actin foci and their movement away from the lamellipodia. The natural retraction of lamellipodia may contribute to B-cell contraction, but the requirement of inner actin foci argues against it as a primary mechanism for B-cell contraction. This study does not exclude the involvement of bundled actin filaments. Based on the requirement of formin-activated bundled actin filaments for lamellipodial F-actin networks and B-cell spreading (Wang et al., 2022), we can speculate that bundled actin filaments may play a role in the formation and movement of these inner F-actin foci, as well as in NMII recruitment.

Our work provides new insights into distinct functions of the actin nucleation-promoting factors WASP and N-WASP in controlling cell morphology and signaling. Immune cells, including B-cells, express both hematopoietic-specific WASP and the ubiquitous homolog of WASP, N-WASP. These two share high sequence homology, activation mechanism, and Arp2/3 activation function (Padrick and Rosen, 2010). We previously identified distinct functions of these two factors unique to B-cells. While both are required for B-cell spreading, N-WASP plays a unique role in B-cell contraction. Wasp and N-wasp double knockout B-cells fail to spread on antigen-presenting surfaces, but B-cell-specific N-wasp knockout enhances B-cell spreading and delays B-cell contraction (Liu et al., 2013a). WASP and N-WASP appear to have a competitive relationship in B-cells, suppressing each other’s activation (Liu et al., 2013a). WASP is activated first during B-cell spreading and is primarily localized at the periphery of the B-cell contact zone. N-WASP is activated later during B-cell contraction and scattered across the B-cell contact zone (Liu et al., 2013a). Here, we reveal the exact role of N-WASP in B-cell contraction – to generate inner F-actin foci from lamellipodial F-actin networks by activating Arp2/3-mediated actin polymerization. N-WASP- but not WASP-activated actin polymerization prolongs the relative lifetime of F-actin foci and facilitates their inward motion toward the center of the contact zone. The delayed activation time and the location in the interior of the contact zone likely give N-WASP a unique opportunity to generate inner F-actin foci. As cNKO only delays and reduces but does not block B-cell contraction and inner F-actin foci formation, other actin factors may be involved, such as the WASP-family verprolin-homologous protein (WAVE) (Rotty et al., 2013).

Our recently published data show that NMII is required for B-cell contraction (Seeley-Fallen et al., 2022). Activated NMII is recruited to the B-cell contact zone in a SHIP-1-dependent manner. NMII levels reach a plateau at the beginning of B-cell contraction, and NMII forms a peripheral ring surrounding the contact zone during B-cell contraction. Here, we further show that in addition to SHIP-1, N-WASP but not WASP is also involved in NMII recruitment and NMII ring-like structure formation, probably by initiating the generation of inner F-actin foci. Collectively, these findings suggest that SHIP-1 coordinates with N-WASP to recruit NMII. Our previous finding that SHIP-1 promotes B-cell contraction by facilitating N-WASP activation (Liu et al., 2011; Liu et al., 2013a) supports this notion. However, it is surprising that the recruitment of NMII activated by BCR signaling to the contact zone is associated with inhibitory signaling molecules. BCR downstream signaling, including Ca²⁺ fluxes and Rho-family GTPase activation, likely activates NMII motor activity (Vicente-Manzanares et al., 2009). The activation switches NMII from the incompetent folded conformation to the competent extended conformation, enabling NMII molecules to bind to F-actin and assemble into contractible bipolar filaments and stacks (Matsumura, 2005). A denser F-actin organization has been shown to increase NMII filament stacking (Fenix and Burnette, 2018). Here, we showed that the inner F-actin foci generated by N-WASP-activated Arp2/3 are more stable and denser and thus likely promote NMII binding and stacking more efficiently than F-actin generated by WASP-activated Arp2/3. Indeed, our kymograph analysis revealed similar time windows and spatial locations for NMII accumulation and for generating inner F-actin foci from lamellipodial F-actin, supporting our hypothesis. While NMII recruitment is facilitated by inner F-actin foci, the motor activity of NMII is required for the formation of the ring-like structures of inner F-actin foci in return, likely by driving their centripetal movement, thereby providing mechanical feedback for actin reorganization. However, the structural organization of inner F-actin foci and recruited NMII and their coordinated dynamics require further analysis with higher-resolution microscopy techniques.

Wang et al., 2022 recently showed that B-cells generate actomyosin arcs when interacting with membrane-associated antigen in the presence of adhesion molecules expressed on professional antigen-presenting cells. In contrast to T-cells, B-cells can also respond to membrane-associated antigens without the help of adhesion molecules, when engaging antigens on pathogenic cells, like bacteria, parasites, and cancer cells. While the relationship between actomyosin arcs and inner F-actin foci remains to be explored, the coordinated formation of inner F-actin foci and NMII ring-like structures revealed in our study suggests that these structures are likely the precursors of actomyosin arcs. These structures can potentially be enhanced and matured by adhesion molecule interactions between B-cells and antigen-presenting membranes.

Our findings suggest an increase in the molecular density within BCR clusters or B-cell synapses as one of the mechanisms by which B-cell contraction promotes BCR signaling attenuation. During contraction, the molecular density of individual BCR clusters, measured by their MFI and peak FI of BCR clustered Fab’, increased faster than during the spreading and post-contraction phases. Surprisingly, increases in molecular density induced disassociation of both the stimulatory kinase Syk and the inhibitory phosphatase SHIP-1, contradicting the existing dogma of sequential association of stimulatory and inhibitory signaling molecules with the BCR (Franks and Cambier, 2018). Interestingly, the disassociation of SHIP-1 is much more sensitive to BCR molecular density than Syk disassociation. Syk does not disassociate until the molecular density of BCR clusters reaches the top 10% range, while SHIP-1 disassociates from BCR clusters with increases over the entire detectable range of molecular densities. When B-cell contraction is inhibited, the molecular density of BCR clusters is reduced to a range with limited Syk disassociation and normal SHIP-1 disassociation, probably resulting in higher Syk to SHIP-1 molecular ratios in BCR clusters than contracting B-cells, increasing BCR signaling levels. The consistency of the data from AF546-Fab’ and pSyk or pSHIP-1 clusters supports this notion. However, the resolution of our widefield TIRF imaging limited our ability to examine nascent BCR clusters that actively recruit signaling molecules. Available antibodies did not allow us to simultaneously stain Syk and SHIP-1 or their phosphorylated forms and determine their relative levels in the same cluster. The timing and dynamics of Syk and SHIP-1 recruitment to individual BCR clusters and the direct relationship between Syk and SHIP-1 association and disassociation with BCR clusters and their phosphorylation remain to be further investigated.

How the molecular density within BCR clusters promotes disassociation of signaling molecules is unknown. We speculate that molecular crowding may displace signaling molecules out of BCR clusters. Supporting this possibility, disassociation of the 145 kDa SHIP-1 is likely to be more sensitive to changes in the molecular density of BCR clusters, compared to disassociation of the 72 kDa Syk. However, these hypotheses need to be further examined. An interesting finding of this study is that the pCD79a and pSyk levels were higher in individual BCR clusters of cNKO B-cells than those of flox control B-cells, even when BCR clusters had similar molecular densities. These data suggest additional mechanisms for B-cell contraction to promote BCR signaling attenuation. In addition to increasing molecular density within BCR clusters, the contractile forces generated by actomyosin rings on the B-cell membrane and BCR clusters may cause changes to the conformations of both BCRs and associated signaling molecules and their lateral interactions in the membrane. These changes may favor the disassociation rather than the association of signaling molecules with BCR clusters. Recently solved molecular assembly structures of both human and mouse BCRs (Dong et al., 2022; Su et al., 2022) support conformational and lateral molecular interaction changes as possible mechanisms for BCR signaling regulation. Similar to the differential impact of the molecular density on the disassociation of Syk and SHIP-1 from BCR clusters, B-cell contraction may differentially affect the interaction of surface BCRs with cytoplasmic and membrane-anchored signaling molecules, such as the lipidated and lipid raft-resident Src kinase Lyn that is responsible for phosphorylating both the immunoreceptor tyrosine-based activation motif (ITAM) of CD79a and the immunoreceptor tyrosine-based inhibitory motif (ITIM) that SHIP-1 binds to (Franks and Cambier, 2018).

Following antigen-induced BCR signaling at immunological synapses, B-cells internalize BCR-captured antigen for processing and presentation. Actomyosin is required for BCR-mediated endocytosis of antigens, particularly surface- and membrane-associated antigens (Natkanski et al., 2013; Hoogeboom et al., 2018; Maeda et al., 2021). NMII-mediated traction forces pull BCR-bound antigen off presenting surfaces for endocytosis in an affinity-dependent manner. We have previously shown that when antigens are tightly attached to a surface, high-affinity binding of the BCR to antigens tears the B-cell membrane in an NMII-dependent manner, which triggers lysosome exocytosis and lysosomal enzyme-mediated cleavages of antigen from the associated surface, allowing antigen endocytosis (Maeda et al., 2021). While actomyosin plays essential roles in both B-cell contraction and the subsequent antigen endocytosis, whether the actomyosin structure responsible for B-cell contraction also mediates BCR endocytosis remains an interesting and open question. Our early finding that N-WASP is required for BCR endocytosis (Liu et al., 2013a) supports this notion. BCR endocytosis can reduce B-cell surface signaling by removing the BCR from the cell surface, transitioning the BCR into an intracellular signaling state (Chaturvedi et al., 2008).

The results presented here have revealed novel insights into the mechanisms underlying actin-facilitated signaling attenuation of the BCR. Taking the previous and current data of our and other labs together, we propose a new working model for such actin-mediated signaling downregulation (Figure 10). Upon encountering membrane-associated antigens, such as antigen presented by follicular dendritic cells and on the surfaces of pathogens, mature follicular B-cells undergo rapid spreading, primarily driven by WASP-mediated branched actin polymerization, which maximizes B-cell contact with antigen-presenting surfaces and BCR-antigen engagement, amplifying signaling. Following maximal spreading, N-WASP distal to lamellipodial networks activates Arp2/3-mediated branched actin polymerization, which initiates the formation of inner F-actin foci from lamellipodia towards the center of the B-cell contact zone (Figure 10). NMII is then preferentially recruited to these relatively stable inner foci, which promotes the centripetal movement of inner F-actin foci and the maturation of ring-like actomyosin structures, enabling B-cell contraction. B-cell contraction pushes the BCR microclusters formed during B-cell spreading to the center of the contact zone, increasing their molecular density. Increased molecular density promotes the disassociation of signaling molecules from BCR clusters, probably due to crowding and conformational changes, leading to signal downregulation (Figure 10). Inhibitory signaling molecules likely activate the actin reorganization that drives B-cell contraction by promoting the activation and recruitment of NMII to the B-cell contact zone (Liu et al., 2013a; Seeley-Fallen et al., 2022) by hitherto unknown mechanisms. The actomyosin structures responsible for B-cell contraction may further drive B-cells to internalize engaged antigen, further downregulating signaling at the B-cell surface and initiating antigen processing and presentation. Thus, actin reorganization downstream of inhibitory phosphatases reinforces signaling attenuation by driving B-cell contraction.

Figure 10

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All data generated or analyzed during this study are included in the manuscript.

1. 1. Adachi T
   2. Wienands J
   3. Wakabayashi C
   4. Yakura H
   5. Reth M
   6. Tsubata T

   (2001) SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates

   The Journal of Biological Chemistry 276:26648–26655.

   https://doi.org/10.1074/jbc.M100997200

   • PubMed
   • Google Scholar
2. 1. Aman MJ
   2. Lamkin TD
   3. Okada H
   4. Kurosaki T
   5. Ravichandran KS

   (1998) The inositol phosphatase SHIP inhibits Akt/PKB activation in B cells

   The Journal of Biological Chemistry 273:33922–33928.

   https://doi.org/10.1074/jbc.273.51.33922

   • PubMed
   • Google Scholar
3. 1. Batista FD
   2. Harwood NE

   (2009) The who, how and where of antigen presentation to B cells

   Nature Reviews. Immunology 9:15–27.

   https://doi.org/10.1038/nri2454

   • PubMed
   • Google Scholar
4. 1. Batista FD
   2. Treanor B
   3. Harwood NE

   (2010) Visualizing a role for the actin cytoskeleton in the regulation of B-cell activation

   Immunological Reviews 237:191–204.

   https://doi.org/10.1111/j.1600-065X.2010.00943.x

   • PubMed
   • Google Scholar
5. 1. Bolger-Munro M
   2. Choi K
   3. Scurll JM
   4. Abraham L
   5. Chappell RS
   6. Sheen D
   7. Dang-Lawson M
   8. Wu X
   9. Priatel JJ
   10. Coombs D
   11. Hammer JA
   12. Gold MR

   (2019) Arp2/3 complex-driven spatial patterning of the BCR enhances immune synapse formation, BCR signaling and B cell activation

   eLife 8:e44574.

   https://doi.org/10.7554/eLife.44574

   • PubMed
   • Google Scholar
6. 1. Bolland S
   2. Pearse RN
   3. Kurosaki T
   4. Ravetch JV

   (1998) SHIP modulates immune receptor responses by regulating membrane association of Btk

   Immunity 8:509–516.

   https://doi.org/10.1016/s1074-7613(00)80555-5

   • PubMed
   • Google Scholar
7. 1. Brauweiler AM
   2. Tamir I
   3. Cambier JC

   (2000) Bilevel control of B-cell activation by the inositol 5-phosphatase SHIP

   Immunological Reviews 176:69–74.

   https://doi.org/10.1034/j.1600-065x.2000.00612.x

   • PubMed
   • Google Scholar
8. 1. Bunnell SC
   2. Kapoor V
   3. Trible RP
   4. Zhang W
   5. Samelson LE

   (2001) Dynamic actin polymerization drives T cell receptor-induced spreading: a role for the signal transduction adaptor LAT

   Immunity 14:315–329.

   https://doi.org/10.1016/s1074-7613(01)00112-1

   • PubMed
   • Google Scholar
9. 1. Carrasco YR
   2. Fleire SJ
   3. Cameron T
   4. Dustin ML
   5. Batista FD

   (2004) LFA-1/ICAM-1 interaction lowers the threshold of B cell activation by facilitating B cell adhesion and synapse formation

   Immunity 20:589–599.

   https://doi.org/10.1016/s1074-7613(04)00105-0

   • PubMed
   • Google Scholar
10. 1. Chaturvedi A
    2. Dorward D
    3. Pierce SK

    (2008) The B cell receptor governs the subcellular location of Toll-like receptor 9 leading to hyperresponses to DNA-containing antigens

    Immunity 28:799–809.

    https://doi.org/10.1016/j.immuni.2008.03.019

    • PubMed
    • Google Scholar
11. 1. Cotta-de-Almeida V
    2. Westerberg L
    3. Maillard MH
    4. Onaldi D
    5. Wachtel H
    6. Meelu P
    7. Chung U
    8. Xavier R
    9. Alt FW
    10. Snapper SB

    (2007) Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development

    PNAS 104:15424–15429.

    https://doi.org/10.1073/pnas.0706881104

    • PubMed
    • Google Scholar
12. 1. Cyster JG

    (2010) B cell follicles and antigen encounters of the third kind

    Nature Immunology 11:989–996.

    https://doi.org/10.1038/ni.1946

    • PubMed
    • Google Scholar
13. 1. Dal Porto JM
    2. Gauld SB
    3. Merrell KT
    4. Mills D
    5. Pugh-Bernard AE
    6. Cambier J

    (2004) B cell antigen receptor signaling 101

    Molecular Immunology 41:599–613.

    https://doi.org/10.1016/j.molimm.2004.04.008

    • PubMed
    • Google Scholar
14. 1. Depoil D
    2. Weber M
    3. Treanor B
    4. Fleire SJ
    5. Carrasco YR
    6. Harwood NE
    7. Batista FD

    (2009) Early events of B cell activation by antigen

    Science Signaling 2:pt1.

    https://doi.org/10.1126/scisignal.263pt1

    • PubMed
    • Google Scholar
15. 1. Dong Y
    2. Pi X
    3. Bartels-Burgahn F
    4. Saltukoglu D
    5. Liang Z
    6. Yang J
    7. Alt FW
    8. Reth M
    9. Wu H

    (2022) Structural principles of B cell antigen receptor assembly

    Nature 612:156–161.

    https://doi.org/10.1038/s41586-022-05412-7

    • PubMed
    • Google Scholar
16. 1. Dustin ML
    2. Starr T
    3. Varma R
    4. Thomas VK

    (2007) Supported planar bilayers for study of the immunological synapse

    Current Protocols in Immunology Chapter 18:18.

    https://doi.org/10.1002/0471142735.im1813s76

    • PubMed
    • Google Scholar
17. 1. Fenix AM
    2. Burnette DT

    (2018) Assembly of myosin II filament arrays: Network Contraction versus Expansion

    Cytoskeleton 75:545–549.

    https://doi.org/10.1002/cm.21487

    • PubMed
    • Google Scholar
18. 1. Fleire SJ
    2. Goldman JP
    3. Carrasco YR
    4. Weber M
    5. Bray D
    6. Batista FD

    (2006) B cell ligand discrimination through a spreading and contraction response

    Science 312:738–741.

    https://doi.org/10.1126/science.1123940

    • PubMed
    • Google Scholar
19. 1. Franks SE
    2. Cambier JC

    (2018) Putting on the brakes: Regulatory kinases and phosphatases maintaining B cell anergy

    Frontiers in Immunology 9:665.

    https://doi.org/10.3389/fimmu.2018.00665

    • PubMed
    • Google Scholar
20. 1. Freeman SA
    2. Lei V
    3. Dang-Lawson M
    4. Mizuno K
    5. Roskelley CD
    6. Gold MR

    (2011) Cofilin-mediated F-actin severing is regulated by the Rap GTPase and controls the cytoskeletal dynamics that drive lymphocyte spreading and BCR microcluster formation

    Journal of Immunology 187:5887–5900.

    https://doi.org/10.4049/jimmunol.1102233

    • PubMed
    • Google Scholar
21. 1. Gitlin AD
    2. Shulman Z
    3. Nussenzweig MC

    (2014) Clonal selection in the germinal centre by regulated proliferation and hypermutation

    Nature 509:637–640.

    https://doi.org/10.1038/nature13300

    • PubMed
    • Google Scholar
22. 1. Gonzalez SF
    2. Pitcher LA
    3. Mempel T
    4. Schuerpf F
    5. Carroll MC

    (2009) B cell acquisition of antigen in vivo

    Current Opinion in Immunology 21:251–257.

    https://doi.org/10.1016/j.coi.2009.05.013

    • PubMed
    • Google Scholar
23. 1. Gross AJ
    2. Lyandres JR
    3. Panigrahi AK
    4. Prak ETL
    5. DeFranco AL

    (2009) Developmental acquisition of the Lyn-CD22-SHP-1 inhibitory pathway promotes B cell tolerance

    Journal of Immunology 182:5382–5392.

    https://doi.org/10.4049/jimmunol.0803941

    • PubMed
    • Google Scholar
24. 1. Hammer JA
    2. Wang JC
    3. Saeed M
    4. Pedrosa AT

    (2019) Origin, organization, dynamics, and function of actin and actomyosin networks at the t cell immunological synapse

    Annual Review of Immunology 37:201–224.

    https://doi.org/10.1146/annurev-immunol-042718-041341

    • PubMed
    • Google Scholar
25. 1. Harwood NE
    2. Batista FD

    (2010) Early events in B cell activation

    Annual Review of Immunology 28:185–210.

    https://doi.org/10.1146/annurev-immunol-030409-101216

    • PubMed
    • Google Scholar
26. 1. Harwood NE
    2. Batista FD

    (2011) The cytoskeleton coordinates the early events of B-cell activation

    Cold Spring Harbor Perspectives in Biology 3:a002360.

    https://doi.org/10.1101/cshperspect.a002360

    • PubMed
    • Google Scholar
27. 1. Hoogeboom R
    2. Tolar P

    (2016) Molecular mechanisms of B cell antigen gathering and Endocytosis

    Current Topics in Microbiology and Immunology 393:45–63.

    https://doi.org/10.1007/82_2015_476

    • PubMed
    • Google Scholar
28. 1. Hoogeboom R
    2. Natkanski EM
    3. Nowosad CR
    4. Malinova D
    5. Menon RP
    6. Casal A
    7. Tolar P

    (2018) Myosin IIa Promotes Antibody Responses by Regulating B Cell Activation, Acquisition of Antigen, and Proliferation

    Cell Reports 23:2342–2353.

    https://doi.org/10.1016/j.celrep.2018.04.087

    • PubMed
    • Google Scholar
29. 1. Kinnon C
    2. Hinshelwood S
    3. Levinsky RJ
    4. Lovering RC

    (1993) X-linked agammaglobulinemia--gene cloning and future prospects

    Immunology Today 14:554–558.

    https://doi.org/10.1016/0167-5699(93)90187-P

    • PubMed
    • Google Scholar
30. 1. Kläsener K
    2. Maity PC
    3. Hobeika E
    4. Yang J
    5. Reth M

    (2014) B cell activation involves nanoscale receptor reorganizations and inside-out signaling by Syk

    eLife 3:e02069.

    https://doi.org/10.7554/eLife.02069

    • PubMed
    • Google Scholar
31. 1. Koestler SA
    2. Auinger S
    3. Vinzenz M
    4. Rottner K
    5. Small JV

    (2008) Differentially oriented populations of actin filaments generated in lamellipodia collaborate in pushing and pausing at the cell front

    Nature Cell Biology 10:306–313.

    https://doi.org/10.1038/ncb1692

    • PubMed
    • Google Scholar
32. 1. Krause M
    2. Gautreau A

    (2014) Steering cell migration: lamellipodium dynamics and the regulation of directional persistence

    Nature Reviews. Molecular Cell Biology 15:577–590.

    https://doi.org/10.1038/nrm3861

    • PubMed
    • Google Scholar
33. 1. Kurosaki T

    (2000) Functional dissection of BCR signaling pathways

    Current Opinion in Immunology 12:276–281.

    https://doi.org/10.1016/s0952-7915(00)00087-x

    • PubMed
    • Google Scholar
34. 1. Kurosaki T
    2. Shinohara H
    3. Baba Y

    (2010) B cell signaling and fate decision

    Annual Review of Immunology 28:21–55.

    https://doi.org/10.1146/annurev.immunol.021908.132541

    • PubMed
    • Google Scholar
35. 1. Kwak K
    2. Akkaya M
    3. Pierce SK

    (2019) B cell signaling in context

    Nature Immunology 20:963–969.

    https://doi.org/10.1038/s41590-019-0427-9

    • PubMed
    • Google Scholar
36. 1. Leung WH
    2. Tarasenko T
    3. Biesova Z
    4. Kole H
    5. Walsh ER
    6. Bolland S

    (2013) Aberrant antibody affinity selection in SHIP-deficient B cells

    European Journal of Immunology 43:371–381.

    https://doi.org/10.1002/eji.201242809

    • PubMed
    • Google Scholar
37. 1. Levayer R
    2. Lecuit T

    (2012) Biomechanical regulation of contractility: spatial control and dynamics

    Trends in Cell Biology 22:61–81.

    https://doi.org/10.1016/j.tcb.2011.10.001

    • PubMed
    • Google Scholar
38. 1. Liu C
    2. Miller H
    3. Hui KL
    4. Grooman B
    5. Bolland S
    6. Upadhyaya A
    7. Song W

    (2011) A balance of Bruton’s tyrosine kinase and SHIP activation regulates B cell receptor cluster formation by controlling actin remodeling

    Journal of Immunology 187:230–239.

    https://doi.org/10.4049/jimmunol.1100157

    • PubMed
    • Google Scholar
39. 1. Liu C
    2. Miller H
    3. Orlowski G
    4. Hang H
    5. Upadhyaya A
    6. Song W

    (2012a) Actin reorganization is required for the formation of polarized B cell receptor signalosomes in response to both soluble and membrane-associated antigens

    Journal of Immunology 188:3237–3246.

    https://doi.org/10.4049/jimmunol.1103065

    • PubMed
    • Google Scholar
40. 1. Liu C
    2. Miller H
    3. Sharma S
    4. Beaven A
    5. Upadhyaya A
    6. Song W

    (2012b) Analyzing actin dynamics during the activation of the B cell receptor in live B cells

    Biochemical and Biophysical Research Communications 427:202–206.

    https://doi.org/10.1016/j.bbrc.2012.09.046

    • PubMed
    • Google Scholar
41. 1. Liu C
    2. Bai X
    3. Wu J
    4. Sharma S
    5. Upadhyaya A
    6. Dahlberg CIM
    7. Westerberg LS
    8. Snapper SB
    9. Zhao X
    10. Song W

    (2013a) N-wasp is essential for the negative regulation of B cell receptor signaling

    PLOS Biology 11:e1001704.

    https://doi.org/10.1371/journal.pbio.1001704

    • PubMed
    • Google Scholar
42. 1. Liu C
    2. Fallen MK
    3. Miller H
    4. Upadhyaya A
    5. Song W

    (2013b) The actin cytoskeleton coordinates the signal transduction and antigen processing functions of the B cell antigen receptor

    Frontiers in Biology 8:475–485.

    https://doi.org/10.1007/s11515-013-1272-0

    • PubMed
    • Google Scholar
43. 1. Maeda FY
    2. van Haaren JJ
    3. Langley DB
    4. Christ D
    5. Andrews NW
    6. Song W

    (2021) Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells

    eLife 10:e66984.

    https://doi.org/10.7554/eLife.66984

    • PubMed
    • Google Scholar
44. 1. Matsumura F

    (2005) Regulation of myosin II during cytokinesis in higher eukaryotes

    Trends in Cell Biology 15:371–377.

    https://doi.org/10.1016/j.tcb.2005.05.004

    • PubMed
    • Google Scholar
45. 1. Mizuno K
    2. Tagawa Y
    3. Mitomo K
    4. Arimura Y
    5. Hatano N
    6. Katagiri T
    7. Ogimoto M
    8. Yakura H

    (2000) Src homology region 2 (SH2) domain-containing phosphatase-1 dephosphorylates B cell linker protein/SH2 domain leukocyte protein of 65 kDa and selectively regulates c-Jun NH2-terminal kinase activation in B cells

    Journal of Immunology 165:1344–1351.

    https://doi.org/10.4049/jimmunol.165.3.1344

    • PubMed
    • Google Scholar
46. 1. Natkanski E
    2. Lee WY
    3. Mistry B
    4. Casal A
    5. Molloy JE
    6. Tolar P

    (2013) B cells use mechanical energy to discriminate antigen affinities

    Science 340:1587–1590.

    https://doi.org/10.1126/science.1237572

    • PubMed
    • Google Scholar
47. 1. Nolen BJ
    2. Tomasevic N
    3. Russell A
    4. Pierce DW
    5. Jia Z
    6. McCormick CD
    7. Hartman J
    8. Sakowicz R
    9. Pollard TD

    (2009) Characterization of two classes of small molecule inhibitors of Arp2/3 complex

    Nature 460:1031–1034.

    https://doi.org/10.1038/nature08231

    • PubMed
    • Google Scholar
48. 1. Padrick SB
    2. Rosen MK

    (2010) Physical mechanisms of signal integration by WASP family proteins

    Annual Review of Biochemistry 79:707–735.

    https://doi.org/10.1146/annurev.biochem.77.060407.135452

    • PubMed
    • Google Scholar
49. 1. Pao LI
    2. Lam KP
    3. Henderson JM
    4. Kutok JL
    5. Alimzhanov M
    6. Nitschke L
    7. Thomas ML
    8. Neel BG
    9. Rajewsky K

    (2007) B cell-specific deletion of protein-tyrosine phosphatase Shp1 promotes B-1a cell development and causes systemic autoimmunity

    Immunity 27:35–48.

    https://doi.org/10.1016/j.immuni.2007.04.016

    • PubMed
    • Google Scholar
50. 1. Peterson JR
    2. Bickford LC
    3. Morgan D
    4. Kim AS
    5. Ouerfelli O
    6. Kirschner MW
    7. Rosen MK

    (2004) Chemical inhibition of N-WASP by stabilization of a native autoinhibited conformation

    Nature Structural & Molecular Biology 11:747–755.

    https://doi.org/10.1038/nsmb796

    • PubMed
    • Google Scholar
51. 1. Pierce SK

    (2002) Lipid rafts and B-cell activation

    Nature Reviews. Immunology 2:96–105.

    https://doi.org/10.1038/nri726

    • PubMed
    • Google Scholar
52. 1. Reth M

    (1994) B cell antigen receptors

    Current Opinion in Immunology 6:3–8.

    https://doi.org/10.1016/0952-7915(94)90026-4

    • PubMed
    • Google Scholar
53. 1. Reth M
    2. Wienands J

    (1997) Initiation and processing of signals from the B cell antigen receptor

    Annual Review of Immunology 15:453–479.

    https://doi.org/10.1146/annurev.immunol.15.1.453

    • PubMed
    • Google Scholar
54. 1. Rey-Suarez I
    2. Wheatley BA
    3. Koo P
    4. Bhanja A
    5. Shu Z
    6. Mochrie S
    7. Song W
    8. Shroff H
    9. Upadhyaya A

    (2020) WASP family proteins regulate the mobility of the B cell receptor during signaling activation

    Nature Communications 11:439.

    https://doi.org/10.1038/s41467-020-14335-8

    • PubMed
    • Google Scholar
55. 1. Riedl J
    2. Flynn KC
    3. Raducanu A
    4. Gärtner F
    5. Beck G
    6. Bösl M
    7. Bradke F
    8. Massberg S
    9. Aszodi A
    10. Sixt M
    11. Wedlich-Söldner R

    (2010) Lifeact mice for studying F-actin dynamics

    Nature Methods 7:168–169.

    https://doi.org/10.1038/nmeth0310-168

    • PubMed
    • Google Scholar
56. 1. Rotty JD
    2. Wu C
    3. Bear JE

    (2013) New insights into the regulation and cellular functions of the ARP2/3 complex

    Nature Reviews. Molecular Cell Biology 14:7–12.

    https://doi.org/10.1038/nrm3492

    • PubMed
    • Google Scholar
57. 1. Schreiner GF
    2. Unanue ER

    (1977)

    Capping and the lymphocyte: models for membrane reorganization

    Journal of Immunology 119:1549–1551.

    • PubMed
    • Google Scholar
58. 1. Seeley-Fallen MK
    2. Liu LJ
    3. Shapiro MR
    4. Onabajo OO
    5. Palaniyandi S
    6. Zhu X
    7. Tan TH
    8. Upadhyaya A
    9. Song W

    (2014) Actin-binding protein 1 links B-cell antigen receptors to negative signaling pathways

    PNAS 111:9881–9886.

    https://doi.org/10.1073/pnas.1321971111

    • PubMed
    • Google Scholar
59. 1. Seeley-Fallen MK
    2. Lazzaro M
    3. Liu C
    4. Li QZ
    5. Upadhyaya A
    6. Song W

    (2022) Non-muscle myosin II is essential for the negative regulation of B-cell receptor signaling and B-cell activation

    Frontiers in Immunology 13:842605.

    https://doi.org/10.3389/fimmu.2022.842605

    • PubMed
    • Google Scholar
60. 1. Sharma S
    2. Orlowski G
    3. Song W

    (2009) Btk regulates B cell receptor-mediated antigen processing and presentation by controlling actin cytoskeleton dynamics in B cells

    Journal of Immunology 182:329–339.

    https://doi.org/10.4049/jimmunol.182.1.329

    • PubMed
    • Google Scholar
61. 1. Shen Z
    2. Liu S
    3. Li X
    4. Wan Z
    5. Mao Y
    6. Chen C
    7. Liu W

    (2019) Conformational change within the extracellular domain of B cell receptor in B cell activation upon antigen binding

    eLife 8:e42271.

    https://doi.org/10.7554/eLife.42271

    • PubMed
    • Google Scholar
62. 1. Shlomchik MJ
    2. Luo W
    3. Weisel F

    (2019) Linking signaling and selection in the germinal center

    Immunological Reviews 288:49–63.

    https://doi.org/10.1111/imr.12744

    • PubMed
    • Google Scholar
63. 1. Skau CT
    2. Waterman CM

    (2015) Specification of architecture and function of actin structures by actin nucleation factors

    Annual Review of Biophysics 44:285–310.

    https://doi.org/10.1146/annurev-biophys-060414-034308

    • PubMed
    • Google Scholar
64. 1. Sohn HW
    2. Tolar P
    3. Pierce SK

    (2008) Membrane heterogeneities in the formation of B cell receptor-Lyn kinase microclusters and the immune synapse

    The Journal of Cell Biology 182:367–379.

    https://doi.org/10.1083/jcb.200802007

    • PubMed
    • Google Scholar
65. 1. Song W
    2. Cho H
    3. Cheng P
    4. Pierce SK

    (1995)

    Entry of B cell antigen receptor and antigen into class II peptide-loading compartment is independent of receptor cross-linking

    Journal of Immunology 155:4255–4263.

    • PubMed
    • Google Scholar
66. 1. Song W
    2. Liu C
    3. Seeley-Fallen MK
    4. Miller H
    5. Ketchum C
    6. Upadhyaya A

    (2013) Actin-mediated feedback loops in B-cell receptor signaling

    Immunological Reviews 256:177–189.

    https://doi.org/10.1111/imr.12113

    • PubMed
    • Google Scholar
67. 1. Su Q
    2. Chen M
    3. Shi Y
    4. Zhang X
    5. Huang G
    6. Huang B
    7. Liu D
    8. Liu Z
    9. Shi Y

    (2022) Cryo-EM structure of the human IgM B cell receptor

    Science 377:875–880.

    https://doi.org/10.1126/science.abo3923

    • PubMed
    • Google Scholar
68. 1. Tanaka S
    2. Baba Y

    (2020) B Cell Receptor Signaling

    Advances in Experimental Medicine and Biology 1254:23–36.

    https://doi.org/10.1007/978-981-15-3532-1_2

    • PubMed
    • Google Scholar
69. 1. Tojkander S
    2. Gateva G
    3. Husain A
    4. Krishnan R
    5. Lappalainen P

    (2015) Generation of contractile actomyosin bundles depends on mechanosensitive actin filament assembly and disassembly

    eLife 4:e06126.

    https://doi.org/10.7554/eLife.06126

    • PubMed
    • Google Scholar
70. 1. Tolar P
    2. Sohn HW
    3. Pierce SK

    (2005) The initiation of antigen-induced B cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer

    Nature Immunology 6:1168–1176.

    https://doi.org/10.1038/ni1262

    • PubMed
    • Google Scholar
71. 1. Tolar P
    2. Hanna J
    3. Krueger PD
    4. Pierce SK

    (2009a) The constant region of the membrane immunoglobulin mediates B cell-receptor clustering and signaling in response to membrane antigens

    Immunity 30:44–55.

    https://doi.org/10.1016/j.immuni.2008.11.007

    • PubMed
    • Google Scholar
72. 1. Tolar P
    2. Sohn HW
    3. Liu W
    4. Pierce SK

    (2009b) The molecular assembly and organization of signaling active B-cell receptor oligomers

    Immunological Reviews 232:34–41.

    https://doi.org/10.1111/j.1600-065X.2009.00833.x

    • PubMed
    • Google Scholar
73. 1. Treanor B
    2. Depoil D
    3. Gonzalez-Granja A
    4. Barral P
    5. Weber M
    6. Dushek O
    7. Bruckbauer A
    8. Batista FD

    (2010) The membrane skeleton controls diffusion dynamics and signaling through the B cell receptor

    Immunity 32:187–199.

    https://doi.org/10.1016/j.immuni.2009.12.005

    • PubMed
    • Google Scholar
74. 1. Unanue ER
    2. Karnovsky MJ

    (1973) Redistribution and fate of Ig complexes on surface of B lymphocytes: functional implications and mechanisms

    Transplantation Reviews 14:184–210.

    https://doi.org/10.1111/j.1600-065x.1973.tb00107.x

    • PubMed
    • Google Scholar
75. 1. Vicente-Manzanares M
    2. Ma X
    3. Adelstein RS
    4. Horwitz AR

    (2009) Non-muscle myosin II takes centre stage in cell adhesion and migration

    Nature Reviews. Molecular Cell Biology 10:778–790.

    https://doi.org/10.1038/nrm2786

    • PubMed
    • Google Scholar
76. 1. Wang H
    2. Morse HC
    3. Bolland S

    (2020) Transcriptional control of mature B cell fates

    Trends in Immunology 41:601–613.

    https://doi.org/10.1016/j.it.2020.04.011

    • PubMed
    • Google Scholar
77. 1. Wang JC
    2. Yim YI
    3. Wu X
    4. Jaumouille V
    5. Cameron A
    6. Waterman CM
    7. Kehrl JH
    8. Hammer JA

    (2022) A B-cell actomyosin arc network couples integrin co-stimulation to mechanical force-dependent immune synapse formation

    eLife 11:e72805.

    https://doi.org/10.7554/eLife.72805

    • PubMed
    • Google Scholar
78. 1. Westerberg LS
    2. Dahlberg C
    3. Baptista M
    4. Moran CJ
    5. Detre C
    6. Keszei M
    7. Eston MA
    8. Alt FW
    9. Terhorst C
    10. Notarangelo LD
    11. Snapper SB

    (2012) Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function

    Blood 119:3966–3974.

    https://doi.org/10.1182/blood-2010-09-308197

    • PubMed
    • Google Scholar
79. 1. Yang J
    2. Reth M

    (2010) Oligomeric organization of the B-cell antigen receptor on resting cells

    Nature 467:465–469.

    https://doi.org/10.1038/nature09357

    • PubMed
    • Google Scholar

Author details

1. Anshuman Bhanja

   Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States

   Present address

   Department of Pharmacology, University of California, San Diego, United States

   Contribution

   Data curation, Software, Formal analysis, Investigation, Visualization, Writing – original draft

   Competing interests

   No competing interests declared

2. Margaret K Seeley-Fallen

   Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States

   Contribution

   Data curation, Writing – review and editing

   Competing interests

   No competing interests declared

3. Michelle Lazzaro

   Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States

   Present address

   AstraZeneca, Gaithersburg, United States

   Contribution

   Data curation

   Competing interests

   No competing interests declared

4. Arpita Upadhyaya

   1. Biophysics Program, University of Maryland, College Park, United States
   2. Department of Physics, University of Maryland, College Park, United States
   3. Institute for Physical Science and Technology, University of Maryland, College Park, United States

   Contribution

   Supervision, Funding acquisition, Writing – review and editing

   For correspondence

   arpitau@umd.edu

   Competing interests

   No competing interests declared

5. Wenxia Song

   Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States

   Contribution

   Conceptualization, Supervision, Funding acquisition, Writing – original draft, Project administration, Writing – review and editing

   For correspondence

   wenxsong@umd.edu

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0001-8795-8657

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