Deretic Nikola, Bolger-Munro Madison, Choi Kate, Abraham Libin, Gold Michael R
Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Front Cell Dev Biol. 2021 Jul 9;9:647063. doi: 10.3389/fcell.2021.647063. eCollection 2021.
Signaling by the B cell antigen receptor (BCR) initiates actin remodeling. The assembly of branched actin networks that are nucleated by the Arp2/3 complex exert outward force on the plasma membrane, allowing B cells to form membrane protrusions that can scan the surface of antigen-presenting cells (APCs). The resulting Arp2/3 complex-dependent actin retrograde flow promotes the centripetal movement and progressive coalescence of BCR microclusters, which amplifies BCR signaling. Glia maturation factor γ (GMFγ) is an actin disassembly-protein that releases Arp2/3 complex-nucleated actin filaments from actin networks. By doing so, GMFγ could either oppose the actions of the Arp2/3 complex or support Arp2/3 complex-nucleated actin polymerization by contributing to the recycling of actin monomers and Arp2/3 complexes. We now show that reducing the levels of GMFγ in human B cell lines via transfection with a specific siRNA impairs the ability of B cells to spread on antigen-coated surfaces, decreases the velocity of actin retrograde flow, diminishes the coalescence of BCR microclusters into a central cluster at the B cell-APC contact site, and decreases APC-induced BCR signaling. These effects of depleting GMFγ are similar to what occurs when the Arp2/3 complex is inhibited. This suggests that GMFγ cooperates with the Arp2/3 complex to support BCR-induced actin remodeling and amplify BCR signaling at the immune synapse.
B细胞抗原受体（BCR）发出的信号启动肌动蛋白重塑。由Arp2/3复合物成核的分支肌动蛋白网络的组装对质膜施加向外的力，使B细胞形成可扫描抗原呈递细胞（APC）表面的膜突起。由此产生的依赖于Arp2/3复合物的肌动蛋白逆行流促进了BCR微簇的向心运动和渐进性聚集，从而放大了BCR信号。神经胶质细胞成熟因子γ（GMFγ）是一种肌动蛋白解聚蛋白，可从肌动蛋白网络中释放由Arp2/3复合物成核的肌动蛋白丝。通过这样做，GMFγ既可以对抗Arp2/3复合物的作用，也可以通过促进肌动蛋白单体和Arp2/3复合物的循环利用来支持由Arp2/3复合物成核的肌动蛋白聚合。我们现在表明，通过用特异性siRNA转染降低人B细胞系中GMFγ的水平会损害B细胞在抗原包被表面上扩散的能力，降低肌动蛋白逆行流的速度，减少BCR微簇在B细胞与APC接触部位聚集成中央簇的现象，并降低APC诱导的BCR信号。耗尽GMFγ的这些作用类似于抑制Arp2/3复合物时发生的情况。这表明GMFγ与Arp2/3复合物协同作用，以支持BCR诱导的肌动蛋白重塑并在免疫突触处放大BCR信号。
