B淋巴细胞活化分子事件及相关病理机制

发布时间：2018-12-14 16:40

【摘要】：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.
[Abstract]:B cell is an important executive cell of humoral immunity, and its activation is the key step to produce protective antibody. At present, the dynamic molecular events and signal initiation mechanisms of early activation of B cells are still unknown. This paper will focus on the application of ultra-high definition imaging and high resolution in vivo imaging in the field of B cells, which will help people to understand the mechanism of early activation of B cells. In this paper, we summarize the progress in the study of the nourishing signal of the B cell receptor (B cell receptor,BCR, which maintains the survival of the B cell in the resting state, and propose several possible models of the source of the nourishing signal. The signal pathway of BCR activation induced by antigen stimulation is described, and the mechanism of initiation of BCR signaling pathway brought about by advances in imaging technology is discussed. Combined with the application of high speed and high resolution living cell imaging in immunology, a series of dynamic processes and the formation of advanced structures during the activation of BCR after antigen stimulation can be captured in real time. In addition, the mechanism of B cell memory immunity was discussed, with emphasis on affinity maturation and BCR subtype transformation. In particular, the intracellular tail of IgG (Immunoglobulin G) type BCR contributes to a rapid and strong memory immune response. Abnormal regulation of the activation mechanism of B cells can disrupt the normal stable balance of B cells and the occurrence of immune diseases. In this paper, the relationship between Fc 纬 RIIB (Fc 纬 receptor IIB) mutation and autoimmune disease, and the relationship between BCR signaling molecular mutation and B cell tumor were summarized. These studies will deepen the understanding of B-cell immune disease and the improvement of medical treatment.
【作者单位】：清华大学生命科学学院教育部蛋白质科学重点实验室;
【基金】：国家重点基础研究发展计划(批准号:2014CB542500-03) 国家高技术研究发展计划(批准号:2014AA020527) 国家自然科学基金(批准号:81361120384,31270913) 北京市自然科学基金(批准号:5132016) 科技部博士点基金(批准号:20130002110059,201200021200076) 教育部新世纪优秀人才支持计划(批准号:NCET-12-0299) 青年千人计划(批准号:2069999-3) 清华大学创新科学研究计划(批准号:2013Z1089279)资助项目
【分类号】：R392

【共引文献】