| Project/Area Number |
13671047
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kumamoto University (2002)
Chiba University (2001) |
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Principal Investigator |
OKADA Seiji Kumamoto Univ. Center for AIDS Research. Div. Of Hematopoiesis, Professor, エイズ学研究センター, 教授 (50282455)
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| Co-Investigator(Kenkyū-buntansha) |
幡野 雅彦 千葉大学, 大学院・医学研究院, 助教授 (20208523)
徳久 剛史 千葉大学, 大学院・医学研究院, 教授 (20134364)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | c-Fos / Bcl6 / Differentiation / macrophage / Memory B cell / C-fos / 造血幹細胞 / BCL6 / BAZF / 転写抑制 / B細胞 |
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| Research Abstract |
Proliferation and differentiation of hematologic cells are regulated by transcriptional factors. We have analyzed role of two immediated early genes, c-Fos and Bcl6.
c-Fos forms AP-1 complex with Jun family and regulates the expression of AP-1 binding genes. Expression of c-fos is induced in normal myelopoiesis. To explore the function of c-fos on myeloid differentiation, we used the murine myeloblastic leukemia cell line M1. Stimulation of M1 cells with LPS promotes their terminal differentiation into functional macrophages. Overexpression of c-fos in M1 cells dramatically increased sensitivity of the cells for LPS-induced differentiation and generation of morphologically differentiated cells. However, the overexpression did not modulate phagocytotic functions, surface expression of macrophage markers such as CD16/CD32 (FcgR) and CD54 (ICAM-1), and expression of lysozyme, esterase and c-fins mRNA. Induction of the class II MHC expression on M1 cells after stimulation was inhibited by t
… More
he overexpression. Expression of CIITA was also reduced in the M1 cells. Overexpression of c-fos in differentiating M1 cells perturbs their functional maturation.
The Bcl6 gene has been identified from the chromosomal translocation breakpoint in B-cell lymphoma and its product functions as a sequence-specific transcriptional repressor. After immunization with T cell-dependent antigens, the high-affinity B cells selected in germinal centers differentiate into memory B cells or long-lived antibody forming cells. We showed that Bcl6-deficient B cells, which cannot develop germinal centers, differentiated into IgM and IgG1 memory B cells but barely into long-lived IgG1 antibody forming cells in the bone marrow. Mutation in the V-heavy gene was nil in these memory B cells. Bcl6 and germinal center formation are essential for somatic hypermutation and affinity maturation, and generation of memory B cells can occur independent of germinal center formation, Ig class-switching and affinity maturation. Less
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