RT Journal Article
SR Electronic
T1 Arp2/3 complex-driven spatial patterning of the BCR enhances immune synapse formation, BCR signaling and cell activation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 490698
DO 10.1101/490698
A1 Madison Bolger-Munro
A1 Kate Choi
A1 Joshua M Scurll
A1 Libin Abraham
A1 Rhys Chappell
A1 Duke Sheen
A1 May Dang-Lawson
A1 Xufeng Wu
A1 John J Priatel
A1 Daniel Coombs
A1 John A Hammer
A1 Michael R Gold
YR 2019
UL http://biorxiv.org/content/early/2019/04/30/490698.abstract
AB 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 remodelling in B cell responses to APC-bound antigens.