Arp2/3 complex-driven spatial patterning of the BCR enhances immune synapse formation, BCR signaling and cell activation
- University of British Columbia, Canada
- National Heart, Lung and Blood Institute, United States
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.
Data availability
Custom image analysis scripts are available online at https://github.com/madscience12/FIJImacros and https://bitbucket.org/jscurll/bolger-munro_image_analysis_scripts/src/780 32434bd6725397459af901000afddab7bd9b58a2?at=master
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Data from: Arp2/3 complex-driven spatial patterning of the BCR enhances immune synapse formation, BCR signaling and cell activationDryad Digital Repository, doi:10.5061/dryad.j1fd7.
Article and author information
Author details
Madison Bolger-Munro
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.
Reviewing Editor
- Michael L Dustin, University of Oxford, United Kingdom
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.
Version history
- Received: December 20, 2018
- Accepted: June 1, 2019
- Accepted Manuscript published: June 3, 2019 (version 1)
- Version of Record published: June 24, 2019 (version 2)
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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Arp2/3 complex-driven spatial patterning of the BCR enhances immune synapse formation, BCR signaling and cell activation
eLife 8:e44574.
https://doi.org/10.7554/eLife.44574
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