Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Outline of Final Research Achievements |
1) We identified plasma cell precursors (Bcl6loIRF4hiCD69hi cells) in germinal center (GC). The generation of these cells requires strong help from T cells via CD40 and sustained interaction with T cells. Fate mapping of GC B cells revealed that in contrast to memory B cells, plasma cells are generated from early to late GCs continuously. 2) We demonstrated that DNA demethylase Tet2 and Tet3 are required for plasma cell generation. Tet2/3-deficient B cells were not able to express high IRF4, which is essential for plasma cell generation. We found the CpG sites in Irf4 locus that are demethylated specifically in plasma cells in Tet2/3-dependent manner. These results suggest that DNA demethylation in these sites are required for high IRF4 expression and subsequent plasma cell generation.
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