A B cell actomyosin arc network couples integrin co-stimulation to mechanical force-dependent immune synapse formation
- National Heart, Lung and Blood Institute, National Institutes of Health, United States
- National Institutes of Allergy and Infectious Diseases, United States
Abstract
B-cell activation and immune synapse (IS) formation with membrane-bound antigens are actin-dependent processes that scale positively with the strength of antigen-induced signals. Importantly, ligating the B-cell integrin, LFA-1, with ICAM-1 promotes IS formation when antigen is limiting. Whether the actin cytoskeleton plays a specific role in integrin-dependent IS formation is unknown. Here we show using super-resolution imaging of mouse primary B cells that LFA-1: ICAM-1 interactions promote the formation of an actomyosin network that dominates the B-cell IS. This network is created by the formin mDia1, organized into concentric, contractile arcs by myosin 2A, and flows inward at the same rate as B-cell receptor (BCR): antigen clusters. Consistently, individual BCR microclusters are swept inward by individual actomyosin arcs. Under conditions where integrin is required for synapse formation, inhibiting myosin impairs synapse formation, as evidenced by reduced antigen centralization, diminished BCR signaling, and defective signaling protein distribution at the synapse. Together, these results argue that a contractile actomyosin arc network plays a key role in the mechanism by which LFA-1 co-stimulation promotes B-cell activation and IS formation.
Data availability
All data generated or analyzed during this study are included in the manuscript and supplementary information. Additionally, Source Data files have been provided for Figure 2 - figure supplement 1B
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Author details
Funding
National Heart, Lung, and Blood Institute (1ZIAHL006121-04)
- John A Hammer III
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations and protocols approved by the National Human Genome Research Institute Animal Use and Care Committee at the National Institutes of Health. All animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#H-0337) of the National Institutes of Health.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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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
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