1. Cell Biology
  2. Immunology and Inflammation
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Arp2/3 complex-driven spatial patterning of the BCR enhances immune synapse formation, BCR signaling and cell activation

  1. Madison Bolger-Munro  Is a corresponding author
  2. Kate Choi
  3. Joshua M Scurll
  4. Libin Abraham
  5. Rhys S Chappell
  6. Duke Sheen
  7. May Dang-Lawson
  8. Xufeng Wu
  9. John J Priatel
  10. Daniel Coombs
  11. John A Hammer
  12. Michael R Gold  Is a corresponding author
  1. University of British Columbia, Canada
  2. National Heart, Lung and Blood Institute, United States
Research Article
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Cite this article as: eLife 2019;8:e44574 doi: 10.7554/eLife.44574

Abstract

When B cells encounter antigens on the surface of an antigen-presenting cell (APC), B cell receptors (BCRs) are gathered into microclusters that recruit signaling enzymes. These microclusters then move centripetally and coalesce into the central supramolecular activation cluster of an immune synapse. The mechanisms controlling BCR organization during immune synapse formation, and how this impacts BCR signaling, are not fully understood. We show that this coalescence of BCR microclusters depends on the actin-related protein 2/3 (Arp2/3) complex, which nucleates branched actin networks. Moreover, in murine B cells this dynamic spatial reorganization of BCR microclusters amplifies proximal BCR signaling reactions and enhances the ability of membrane-associated antigens to induce transcriptional responses and proliferation. Our finding that Arp2/3 complex activity is important for B cell responses to spatially-restricted membrane-bound antigens, but not for soluble antigens, highlights a critical role for Arp2/3 complex-dependent actin remodeling in B cell responses to APC-bound antigens.

Article and author information

Author details

  1. Madison Bolger-Munro

    Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    For correspondence
    mbolgerm@mail.ubc.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8176-4824
  2. Kate Choi

    Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Joshua M Scurll

    Department of Mathematics, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Libin Abraham

    Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Rhys S Chappell

    Department of Mathematics, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Duke Sheen

    Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. May Dang-Lawson

    Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Xufeng Wu

    Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. John J Priatel

    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  10. Daniel Coombs

    Department of Mathematics, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8038-6278
  11. John A Hammer

    Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Michael R Gold

    Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    For correspondence
    mgold@mail.ubc.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1222-3191

Funding

Canadian Institutes of Health Research (MOP-68865)

  • Michael R Gold

Natural Sciences and Engineering Research Council of Canada (RGPIN-2015-04611)

  • Daniel Coombs

Canadian Institutes of Health Research (PJT-152946)

  • Michael R Gold

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All of the animals were handled according to protocols approved by the University of British Columbia Animal Care Committee. Our animal protocols were approved by the University of British Columbia Animal Care Committee (mouse breeding license #A18-0334; animal use license #A15-0162). Mice were euthanized using halothane inhalation, followed by cervical dislocation, as detailed in our approved animal licenses.

Reviewing Editor

  1. Michael L Dustin, University of Oxford, United Kingdom

Publication history

  1. Received: December 20, 2018
  2. Accepted: June 1, 2019
  3. Accepted Manuscript published: June 3, 2019 (version 1)

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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