| Project/Area Number |
24790481
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | Sapporo Medical University (2013)
Tokyo University of Science (2012) |
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Principal Investigator |
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| Research Collaborator |
GOITSUKA Ryo 東京理科大学, 生命医科学研究所, 教授 (50301552)
AZUMA Takachika 東京理科大学, 生命医科学研究所, 教授 (00028234)
MURAKAMI Akikazu 琉球大学, 大学院医学研究科, 助教 (00733635)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 免疫寛容 / 自己免疫 / 抗体 / 自己免疫疾患 / 自己抗体 / クラススイッチ / 体細胞突然変異 / B細胞 |
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| Research Abstract |
Conditional B cell-specific knockout of pKnox1, a homeodomain transcription factor, in mice leads to age-associated development of autoimmune phenotypes. In order to understand the molecular basis, we analyzed B cell development and immune responses. The mice showed abnormal marginal zone B cell development, decreased IgG level, delayed affinity maturation caused by decreased frequency of somatic hypermutation and delayed germinal center formation. The expression level of AID (Activation-induced cytidine deaminase) was decreased in the mice compared with control mice. The expression level of HoxC4 that directly regulates AID expression also decreased. We found the sequence that is similar to pKonox1-Pbx1 complex binding domain in HoxC4 promoter, too. These findings indicate that the autoimmune phenotypes in B cell–specific knockout of pKnox1 mice might be related to the failure of AID expression regulatory mechanisms.
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