B淋巴细胞免疫活化的早期信号转导研究  

Early molecular events in B lymphocyte activation

作　　者：沈志勋 刘思辰 曾颖玥 刘万里[1] SHEN Zhi-Xun;LIU Si-Chen;ZENG Ying-Yue;LIU Wan-Li(School of Life Sciences,Tsinghua University,Beijing 100084,China)

机构地区：[1]清华大学生命科学学院

出　　处：《中国免疫学杂志》2019年第13期1537-1543,共7页Chinese Journal of Immunology

摘　　要：B细胞作为体液免疫的重要组成部分,通过其表面分布的B细胞受体(BCR)识别外界抗原,是机体产生保护性抗体及免疫记忆的关键步骤。过去几十年间,利用传统的生化及遗传方法,BCR与抗原结合后所激活的复杂信号通路已被广泛研究。近年来,随着高速高分辨活细胞成像技术的快速发展,人们开始关注B细胞活化早期,尤其是BCR结合抗原后几十秒内的各类分子事件。这些B细胞活化早期分子事件对下游信号通路起始及B细胞活化效率有至关重要的影响。本文首先探讨静息态下B细胞质膜上的BCR存在状态,及其如何产生滋养信号以维持B细胞的生存。重点描述了BCR活化早期分子事件的现有研究,及基于已有研究结果总结出的BCR早期活化分子模型。此外,本文也综述B细胞产生免疫记忆的机制,尤其是活化早期分子事件如何促进表达IgG型BCR的记忆性B细胞快速高效活化。最后,本文总结B细胞早期活化异常与自身免疫疾病、B细胞肿瘤等疾病的关联,介绍这些研究如何帮助人们更深入地理解B细胞相关疾病的致病机制,并促进新的防治手段的开发。B lymphocytes (B cells) are the fundamental parts of humoral immunity by recognizing external antigens through B cell receptors (BCRs),which is a key step to produce protective antibodies and to generate immune memory.Over the past few decades,complex signaling pathways triggered by antigen binding to BCR have been extensively studied through traditional biochemical and genetic approaches.In recent years,with the development of high-speed high-resolution live cell imaging technology,intense efforts have been focused on molecular events occurring in the early stage of B cell activation,especially within the first few seconds after BCR interacts with antigen.These early molecular events have a critical impact on the initiation of downstream signaling pathways and the outcome of B cell activation.In this review,we firstly discussed the status of BCRs in resting B cell and how these resting BCRs produce a tonic signal to maintain B cell survival.Existing studies on early molecular events during BCR activation and several proposed models based on these findings were also described to explain the initiation of B cell activation.The mechanisms by which B cell memory is produced are also discussed,especially the early molecular events in the initiation of B cell expressing IgG-BCR signaling and how these events contribute to the fast and efficient activation of IgG B cell.Finally,we introduced the associations between aberrant regulation of B cell early activation and diseases,such as autoimmune diseases and B cell tumors.These studies may improve our understanding of the pathogenesis of B cell-related diseases and promote the development of new prevention and treatment strategy.

关 键 词：B细胞 B细胞受体 B细胞活化 免疫突触 分子成像 

分 类 号：R291[医药卫生—民族医学]