Study for Development and Maintenance of mune Memory

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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.