Hoogeboom Robbert, Tolar Pavel
Division of Immune Cell Biology, National Institute for Medical Research, Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, London, NW7 1AA, UK.
Curr Top Microbiol Immunol. 2016;393:45-63. doi: 10.1007/82_2015_476.
Generation of high-affinity, protective antibodies requires B cell receptor (BCR) signaling, as well as antigen internalization and presentation to helper T cells. B cell antigen internalization is initiated by antigen capture, either from solution or from immune synapses formed on the surface of antigen-presenting cells, and proceeds via clathrin-dependent endocytosis and intracellular routing to late endosomes. Although the components of this pathway are still being discovered, it has become clear that antigen internalization is actively regulated by BCR signaling at multiple steps and, vice versa, that localization of the BCR along the endocytic pathway modulates signaling. Accordingly, defects in BCR internalization or trafficking contribute to enhanced B cell activation in models of autoimmune diseases and in B cell lymphomas. In this review, we discuss how BCR signaling complexes regulate each of the steps of this endocytic process and why defects along this pathway manifest as hyperactive B cell responses in vivo.
产生高亲和力的保护性抗体需要B细胞受体（BCR）信号传导，以及抗原内化和呈递给辅助性T细胞。B细胞抗原内化由抗原捕获启动，抗原捕获可来自溶液或抗原呈递细胞表面形成的免疫突触，并通过网格蛋白依赖性内吞作用和细胞内转运至晚期内体进行。尽管该途径的组成成分仍在被发现，但很明显，抗原内化在多个步骤中受到BCR信号传导的积极调控，反之亦然，即BCR沿内吞途径的定位调节信号传导。因此，在自身免疫性疾病模型和B细胞淋巴瘤中，BCR内化或运输缺陷导致B细胞活化增强。在本综述中，我们讨论了BCR信号复合物如何调节这一内吞过程的各个步骤，以及为什么该途径中的缺陷在体内表现为B细胞反应过度活跃。
