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Study for Development and Maintenance of mune Memory

记忆力的发展和维持研究

基本信息

批准号：
15078202
负责人：
TOKUHISA Takeshi
金额：
$ 90.88万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

项目摘要

High affinity memory B cells can be generated from germinal centers (GCs) in the secondary lymphoid organs. Somatic hypermutation in the V-gene, which is critical for the generation of high-affinity antibodies, and Ig class switch recombination occur in GC B cells. These high affinity GC B cells differentiate to memory B cells or long-lived plasma cells. We have been studied roles of transcription factors, BcI6 and and os/AP-1, in these differentiation processes of GC B cells.1. The promoter region of the murine BcI6 gene has been studied. JunD/AP-1 and activated STAT factors drive high BcI6 expression in GC B cells. Since stimulation of splenic B cells with IL-21 induced high BcI6 expression with induction of junD and activation of STAT factors, IL-21 may be a major inducer for high BcI6 expression in GC B cells.2. When B cells were sequentially stimulated with anti-IgM Ab and antiCD40 Ab plus IL-4 and then with IL-21 at a two day interval, proliferation, frequency of class switch to IgG1 and plasma cell differentiation were continuously enhanced. Since BcI6-deficient B cells were stimulated with the protocol, proliferation and frequency of class switch to IgG1 of the Be 16eficient B cells were about half of those of the wild-type B cells, suggesting that these in vitro activated B cells contain GC B cells.3. Expression of Blimp-1 transcription factor is essential for promoting B cell differentiation into plasma cells, and overexpression of cos induced a sufficient amount of blimp-1 for terminal differentiation in H2os B cells. Thus, although cos is not essential for blimp-1 expression, cos/AP-1 positively regulates blimp-1 expression and terminal differentiation of activated B cells.

高亲和力记忆B细胞可以从次级淋巴器官中的生发中心（GC）产生。在GC B细胞中，V基因的体细胞超突变和IG类转换重组发生，V基因对于产生高亲和力抗体至关重要。这些高亲和力GC B细胞分化为记忆B细胞或长寿浆细胞。我们研究了转录因子Bcl 6和os/AP-1在胃癌B细胞分化过程中的作用.对鼠BcI 6基因的启动子区进行了研究。JunD/AP-1和激活的STAT因子驱动GC B细胞中的高Bcl 6表达。结论：1. IL-21刺激脾B细胞可诱导Bcl-6的高表达，并诱导junD和STAT因子的激活，IL-21可能是GC B细胞Bcl-6高表达的主要诱导剂.当B细胞依次用抗IgM抗体和抗CD 40抗体加IL-4刺激，然后用IL-21刺激，间隔两天，增殖、向IgG 1类转换的频率和浆细胞分化持续增强。用该方案刺激BcI 6缺陷型B细胞，BcI 6有效型B细胞的增殖和向IgG 1类转换的频率约为野生型B细胞的一半，表明这些体外活化的B细胞中含有GC B细胞. Blimp-1转录因子的表达对于促进B细胞分化为浆细胞是必需的，并且cos的过表达诱导足够量的Blimp-1用于H2os B细胞中的终末分化。因此，尽管cos对blimp-1表达不是必需的，但cos/AP-1正调节blimp-1表达和活化的B细胞的终末分化。