| Project/Area Number |
15390095
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
IGARASHI Kazuhiko Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (00250738)
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| Co-Investigator(Kenkyū-buntansha) |
TASHIRO Satoshi Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射線医科学研究所, 教授 (20243610)
MUTO Akihiko Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (80343292)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2004: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2003: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | Bach1 / Bach2 / transcription factor / globin / B cell / heme / oxidative stress / Maf |
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| Research Abstract |
For the sake of clarity, I shall give a summary of the analysis of B cell system below.
Activated B cells differentiate to plasma cells to secrete immunoglobulin MI (IgM) or, after undergoing class switch recombination (CSR), to secrete other classes of immunoglobulins. Diversification of antibody function by CSR is important for humoral immunity. However, it remains unclear how the decision for the bifurcation is made. Bach2 is a B cell-specific transcription repressor interacting with the small Maf proteins whose expression is high only prior to plasma cell stage. Here we report that Bach2 is critical for CSR and somatic hypermutation (SHM) of immunoglobulin genes. Genetic ablation of bach2 in mice revealed that Bach2 was required for both T cell-independent and -dependent IgG responses and SHM. When stimulated in vitro, Bach2-deficient B cells produced IgM as did wild-type cells and expressed abundantly Blimp-1 and XBP-1, critical regulators of the plasmacytic differentiation, suggesting that Bach2 was not required for the plasmacytic differentiation per se. However, they failed to undergo efficient CSR. These findings define Bach2 as a key regulator of antibody response and provide an insight into the orchestration of CSR and SHM during plasma cell differentiation.
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