| Project/Area Number |
12557046
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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 | 展開研究 |
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| Research Field |
内科学一般
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| Research Institution | Chiba University |
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Principal Investigator |
TOKUHISA Takeshi Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (20134364)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Seiji Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (50282455)
HATANO Masahiko Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (20208523)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2001: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2000: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | BCL6 / Allergic inflammation / Germinal center / Memory B cells / Transgenic mice / IL-5 / Gene therapy / Eosinophil / 疾患モデルマウス / IgE産生メモリーB細胞 / Bcl6 / Th1細胞 / サイトカイン / 好酸球性アレルギー炎症 |
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| Research Abstract |
BCL6-KO mice display no germinal center formation and severe allergic inflammation with eosinophilic infiltration. We found that one of the target gene of BCL6 in T cells is the IL-5 gene. In this project, we investigated the functional role of BCL6 in memory B cell development and tried to develop the gene therapy model for allergic diseases by establishing model animals in which expression of BCL6 is controlled. We show that (1) BCL6-KO mice produced control levels of secondary IgG1 antibodies, and generated transferable IgG1 memory B cells in the spleen. Mutation in the V-hedvy gene was nil in those memory B cells. We have established transgenic mice carrying the Ig-BCL6, and the germinal center formation and memory responses were augmented in transgenic mice. Therefore, Bcl6 is essential for somatic hypermutation and generation of memory B cells in germinal centers. (2) We have established transgenic mice carrying the lck-BCL6 gene. When splenic T cells from lck-BCL6 mice were stimulated with anti-CD3 antibody, IL-5 production was specifically suppressed. Those lck-BCL6 mice were mated with BCL6-KO mice and the allergic inflammation in BCL6-KO mice was completely controlled. We have established the gene transfer method using virus vectors. We wish to develop the efficient gene therapy method for allergic diseases near future.
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