| Project/Area Number |
26670239
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
Kitamura Daisuke 東京理科大学, 研究推進機構生命医科学研究所, 教授 (70204914)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 免疫学 / 体細胞突然変異 / 胚中心 / B細胞 / 抗体 |
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| Outline of Final Research Achievements |
Activation-induced deaminase (AID) is essential for both somatic hypermutation (SHM) and class switch recombination (CSR), contributing to antibody affinity maturation. Although both occurs in germinal center (GC) B cells, only CSR is induced in B cells cultured with mitogen, expressing AID. Therefore some mechanism works in germinal center B cells to induce SHM but not in cultured B cells.
We utilized the system called iGB cell culture, in which naive B cells are cultured on feeder cells with IL-4 or IL-21. The cultured B cells greatly proliferate, acquire GC phenotype and undergo CSR, but not SHM. However, memory B cells cultured similarly with Ag stimulation undergo SHM. Blimp1-deficient B cells accumulated even more SHM. Introduction of Bcl6 enabled B cells to proliferate for more than 2 months with accumulating SHM, but eventually only clones with a dominant nuclear AID kept undergoing SHM.
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