| Project/Area Number |
15078202
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Chiba University |
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Principal Investigator |
TOKUHISA Takeshi Chiba University, Graduate School of Medicine, Professor, 大学院医学研究院, 教授 (20134364)
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| Co-Investigator(Kenkyū-buntansha) |
竹森 利忠 国立感染症研究所, 免疫部, 部長 (60114295)
木下 和生 京都大学, 大学院・医学研究科, 助教授 (50293874)
坂本 明美 千葉大学, 大学院・医学研究院, 助手 (90359597)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥142,000,000 (Direct Cost: ¥142,000,000)
Fiscal Year 2006: ¥27,800,000 (Direct Cost: ¥27,800,000)
Fiscal Year 2005: ¥27,800,000 (Direct Cost: ¥27,800,000)
Fiscal Year 2004: ¥26,400,000 (Direct Cost: ¥26,400,000)
Fiscal Year 2003: ¥60,000,000 (Direct Cost: ¥60,000,000)
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| Keywords | Allergy / CO Gene / Infectious Disease / Transcription / Immunology / Immune Memory Cell / Transcription Factor / Transgenic Technology / BCL6 / AP-1 / STAT3 / c-Fos / Blimp-1 / 胚中心B細胞 / IL-21 / Follicular helper T cell / 体細胞突然変異 / ADAR1 / クラススイッチ / 遺伝子欠損マウス / メモリーT細胞 / メモリーB細胞 / 癌 / ゲノム |
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| Research Abstract |
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.
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