Immune Receptor Activation Laboratory, The Francis Crick Institute, London, United Kingdom.
Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London, United Kingdom.
Elife. 2019 Dec 9;8:e48093. doi: 10.7554/eLife.48093.
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.
抗体的产生依赖于 B 细胞对内源抗原的内化和呈递给辅助性 T 细胞。为了获取抗原呈递细胞所呈递的抗原，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性提取抗原。虽然已经研究了细胞骨架组织驱动 B 细胞突触的初始形成，但细胞骨架如何支持抗原的提取仍知之甚少。在这里，我们发现，在初始细胞铺展后，原代小鼠 B 细胞和人 B 细胞系中的 F-actin 形成了一种高度动态的模式，由肌动蛋白焦点与线性丝和肌球蛋白 IIa 交错组成。这些焦点是由 Arp2/3 介导的分支肌动蛋白聚合产生的，并与抗原簇随机结合以介导内化。然而，抗原的提取还需要形成蛋白的活性，它们位于焦点附近，并产生交错的丝。因此，分支肌动蛋白焦点在线性丝的支持下，为 B 细胞在抗原提取过程中的力学提供了基础。
