4.6 Article

WAVE2 Regulates Actin-Dependent Processes Induced by the B Cell Antigen Receptor and Integrins

期刊

CELLS
卷 12, 期 23, 页码 -

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MDPI
DOI: 10.3390/cells12232704

关键词

B cell; B cell antigen receptor (BCR); antigen presenting cell (APC); F-actin; WAVE2; Arp2/3 complex; cell spreading; immune synapse

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The study reveals that WAVE2 plays a crucial role in B lymphocytes by participating in actin cytoskeleton remodeling, cell spreading, BCR signal amplification, and immune response.
B cell antigen receptor (BCR) signaling induces actin cytoskeleton remodeling by stimulating actin severing, actin polymerization, and the nucleation of branched actin networks via the Arp2/3 complex. This enables B cells to spread on antigen-bearing surfaces in order to increase antigen encounters and to form an immune synapse (IS) when interacting with antigen-presenting cells (APCs). Although the WASp, N-WASp, and WAVE nucleation-promoting factors activate the Arp2/3 complex, the role of WAVE2 in B cells has not been directly assessed. We now show that both WAVE2 and the Arp2/3 complex localize to the peripheral ring of branched F-actin when B cells spread on immobilized anti-Ig antibodies. The siRNA-mediated depletion of WAVE2 reduced and delayed B cell spreading on immobilized anti-Ig, and this was associated with a thinner peripheral F-actin ring and reduced actin retrograde flow compared to control cells. Depleting WAVE2 also impaired integrin-mediated B cell spreading on fibronectin and the LFA-1-induced formation of actomyosin arcs. Actin retrograde flow amplifies BCR signaling at the IS, and we found that depleting WAVE2 reduced microcluster-based BCR signaling and signal amplification at the IS, as well as B cell activation in response to antigen-bearing cells. Hence, WAVE2 contributes to multiple actin-dependent processes in B lymphocytes.

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