B cells extract antigens at Arp2/3-generated actin foci interspersed with linear filaments
B cells extract antigens at Arp2/3-generated actin foci interspersed with linear filaments
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DOI：
10.7554/elife.48093
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发表时间：
2019-12-09
期刊：
影响因子：
7.7
通讯作者：
Tolar, Pavel
中科院分区：
文献类型：
--
作者：
Roper, Sophie I.;Wasim, Laabiah;Tolar, Pavel
抗体的产生取决于 B 细胞内化和向辅助 T 细胞呈递抗原。为了获取抗原呈递细胞展示的抗原，B 细胞形成免疫突触并通过肌动球蛋白细胞骨架的机械活动提取抗原。虽然驱动 B 细胞突触初始形成的细胞骨架组织已被研究，但细胞骨架如何支持抗原提取仍知之甚少。在这里，我们表明，在初始细胞扩散后，原代小鼠 B 细胞和人 B 细胞系突触中的 F-肌动蛋白形成由散布线性丝和肌球蛋白 IIa 的肌动蛋白灶组成的高度动态模式。这些焦点是由 Arp2/3 介导的分支肌动蛋白聚合产生的，并与抗原簇随机关联以介导内化。然而，抗原提取还需要福尔明的活性，福尔明位于病灶附近并产生散布的细丝。因此，线性丝支持的分支肌动蛋白焦点的协作是抗原提取过程中 B 细胞力学的基础。
Antibody production depends on B cell internalization and presentation of antigens to helper T cells. To acquire antigens displayed by antigen-presenting cells, B cells form immune synapses and extract antigens by the mechanical activity of the acto-myosin cytoskeleton. While cytoskeleton organization driving the initial formation of the B cell synapse has been studied, how the cytoskeleton supports antigen extraction remains poorly understood. Here we show that after initial cell spreading, F-actin in synapses of primary mouse B cells and human B cell lines forms a highly dynamic pattern composed of actin foci interspersed with linear filaments and myosin IIa. The foci are generated by Arp2/3-mediated branched-actin polymerization and stochastically associate with antigen clusters to mediate internalization. However, antigen extraction also requires the activity of formins, which reside near the foci and produce the interspersed filaments. Thus, a cooperation of branched-actin foci supported by linear filaments underlies B cell mechanics during antigen extraction.