eLife | |
Arp2/3 complex-driven spatial patterning of the BCR enhances immune synapse formation, BCR signaling and B cell activation | |
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[1] Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States;Department of Mathematics, Institute of Applied Mathematics, University of British Columbia, Vancouver, Canada;Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada;Life Sciences Institute, I3 Research Group, University of British Columbia, Vancouver, Canada;Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada;Life Sciences Institute, I3 Research Group, University of British Columbia, Vancouver, Canada;Department of Mathematics, Institute of Applied Mathematics, University of British Columbia, Vancouver, Canada;Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada;BC Children’s Hospital Research Institute, Vancouver, Canada; | |
关键词: Arp2/3 complex; actin dynamics; B cell; B cell receptor; immune synapse; antigen-presenting cell; Mouse; | |
DOI : 10.7554/eLife.44574 | |
来源: publisher | |
【 摘 要 】
10.7554/eLife.44574.001When 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.
【 授权许可】
CC BY
【 预 览 】
Files | Size | Format | View |
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RO201911197967817ZK.pdf | 8806KB | download |