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WAVE2 调控 B 细胞抗原受体和整合素诱导的肌动蛋白依赖过程。

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

机构信息

Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T1Z3, Canada.

出版信息

Cells. 2023 Nov 25;12(23):2704. doi: 10.3390/cells12232704.

Abstract

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.

摘要

B 细胞抗原受体 (BCR) 信号通过刺激肌动蛋白的分裂、聚合和通过 Arp2/3 复合物引发分支肌动蛋白网络的成核来诱导肌动蛋白细胞骨架重塑。这使 B 细胞能够在抗原存在的表面上扩散,以增加抗原的接触,并在与抗原呈递细胞 (APC) 相互作用时形成免疫突触 (IS)。尽管 Wasp、N-WASp 和 WAVE 成核促进因子激活了 Arp2/3 复合物,但 WAVE2 在 B 细胞中的作用尚未得到直接评估。我们现在表明,当 B 细胞在固定化抗 Ig 抗体上扩散时,WAVE2 和 Arp2/3 复合物都定位在分支 F-肌动蛋白的外周环上。用 siRNA 介导的 WAVE2 耗竭减少并延迟了固定化抗 Ig 上的 B 细胞扩散,与对照细胞相比,这与外周 F-肌动蛋白环变薄和肌动蛋白逆行流动减少有关。WAVE2 的耗竭也损害了整合素介导的 B 细胞在纤维连接蛋白上的扩散和 LFA-1 诱导的肌动球蛋白弧的形成。肌动蛋白逆行流动在 IS 处放大 BCR 信号,我们发现耗竭 WAVE2 减少了基于微簇的 BCR 信号和 IS 处的信号放大,以及抗原呈递细胞刺激下的 B 细胞激活。因此,WAVE2 有助于 B 淋巴细胞中的多种依赖肌动蛋白的过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40a5/10705906/9fb6866fa9a5/cells-12-02704-g001.jpg

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