B淋巴细胞活化分子事件及相关病理机制

B细胞是体液免疫的重要执行细胞,其活化是机体产生保护性抗体的关键步骤.目前人们对B细胞早期活化的动态分子事件和信号起始机制等仍然未知.本文将重点总结超高清成像技术和高速高分辨率活体成像技术在B细胞领域的应用,这些研究将帮助人们理解B细胞早期活化的机制.本文系列总结了静息态下维持B细胞存活的B细胞受体(B cell receptor,BCR)滋养信号的研究进展,并提出了滋养信号来源的几种可能的模型.描述了抗原刺激导致的BCR活化的信号通路,并重点探讨了成像技术进步带来的关于BCR信号通路起始的机制探索这一免疫学领域的重大问题.结合高速高分辨率活细胞成像技术在免疫学领域的应用,抗原刺激后BCR活化过程中一系列动态变化过程和高级结构的形成能够被实时捕获.此外,还探讨了B细胞记忆性免疫发生的机制,重点阐述了亲和力成熟和BCR亚型转换,尤其是IgG(Immunoglobulin G)型BCR胞内尾巴对快速强烈的记忆性免疫反应的帮助.B细胞活化机制的调节过程发生异常会破坏正常的B细胞稳态平衡和免疫疾病的发生,本文总结抑制性调节受体FcγRIIB(Fcγreceptor IIB)突变与自身免疫病的关系,以及BCR信号通路信号分子突变与B细胞肿瘤的关系,这些研究将加深人们对B细胞免疫疾病的认识和相应医疗手段的改进.

Molecular Mechanism of B Lymphocyte Activation and the Associated Diseases

B cells are important immune cells for humoral immune responses. B cell activation is a critical step for antibody production in response to pathogen invasion. In this review, we focused on the recent achievements in B cell studies using high-resolution high-speed live cell imaging techniques. These studies substantially improve our understanding of the molecular events governing the initiation of B cell activation. We summarized the recent studies about tonic B cell receptor （BCR） signaling which is thought to be responsible for B cell survival. We proposed several models to explain the origin of tonic BCR signaling. Meanwhile, we described the BCR signaling pathway driven by antigen stimulation, and discussed the possible mechanisms initiating B cell activation. Especially, we described how the high-resolution high-speed live cell imaging techniques help scientists to capture the dynamic events during B cell activation. Moreover, we discussed the molecular nature of the memory B cell with special focus placed on the roles of the evolutionarily conserved IgG cytoplasmic tail in memory antibody responses. Abnormal regulation of BCR activation may lead to diseases. In this regard, we discussed the recent findings in the last part of this review and also summarized the relationship of the mutation in the BCR inhibitory co-receptor FcyRIIB and autoimmune diseases. Furthermore, we discussed the relationship between the mutation in BCR signaling molecules and B cell tumor. This work improves our understanding about B cell diseases and may benefit the clinical therapy.