Project/Area Number |
60065006
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Research Category |
Grant-in-Aid for Specially Promoted Research
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Allocation Type | Single-year Grants |
Research Institution | Institute for Molecular and Cellular Biology, Osaka University |
Principal Investigator |
KISHIMOTO Tadamitsu Professor, Inst. Molec. & Cell. Biology, Osaka University, 細胞工学センター, 教授 (10093402)
|
Co-Investigator(Kenkyū-buntansha) |
AKIRA Shizuo Associate Professor, Inst. Molec. & Cell. Biology, Osaka University, 細胞工学センター, 助手 (50192919)
KIKUTANI Hitoshi Associate Professor, Inst. Molec. & Cell. Biology, Osaka University, 細胞工学センター, 助手 (80161412)
HIRANO Toshio Associate Professor, Inst. Molec. & Cell. Biology, Osaka University, 細胞工学センター, 助教授 (40136718)
村口 篤 大阪大学, 細胞工学センター, 助手 (20174287)
|
Project Period (FY) |
1985 – 1988
|
Project Status |
Completed (Fiscal Year 1988)
|
Budget Amount *help |
¥186,000,000 (Direct Cost: ¥186,000,000)
Fiscal Year 1988: ¥42,000,000 (Direct Cost: ¥42,000,000)
Fiscal Year 1987: ¥48,000,000 (Direct Cost: ¥48,000,000)
Fiscal Year 1986: ¥48,000,000 (Direct Cost: ¥48,000,000)
Fiscal Year 1985: ¥48,000,000 (Direct Cost: ¥48,000,000)
|
Keywords | Interleukin 6 (IL-6) / B cell stimulatory factor 2 (BSF2) / plasmacytoma growth factor / Fcepsilon receptor (FcepsilonRII) / Fcεレセプター / CD23 / IL-6 / IL-6レセプターcDNA / FcεRII / FcεRIIaとFcεRIIb / IL-4 / BiF2 / 肝細胞刺激因子 / 抗IL6抗体 / Fcrレセプター / BSF2 / 抗体産生 / 自己免疫疾患 / IFNβ2 / アトピー / EBV / Bリンパ球の増殖と分化 / Bリンパ球分因子(BCDF) / 部分アミノ酸配列 / 抗ペプチド抗体Myxoma / 活性化Bリンパ球 / Bリンパ球増殖因子(BCGF) / Two colour FACS解析 |
Research Abstract |
Interleukin 6 was originally identified as T cell-derived lymphokine which induced final differentiation of B cells and its cDNA was cloned. The study with recombinant IL-6 confirmed that IL-6 was one of the essential factor for B cells to produce antibody molecules. However, the studies demonstrated that IL-6 acted not only on B cells but showed a wide variety of biological functions on varions tissues and cells. For example it acts on T cells as cytotoxic T cell differentiation factor, on hematopoietic stem cells as multi-colony stimulating factor, on hepatocytes to induce acute phase proteins. It functions as myeloma/plasmacytoma growth factor and the result with myeloma cells from patients demonstrated that il-6 functioned as an autocrine growth factor for myeloma cells. Transgenic mice with human IL-6 gene generated plasmacytomas confirming that constitutive expression of IL-6 in B lineage cells in involved in oncogenesis of myeloma/plasmacytoma. The cDNA encoding for IL-6 receptor was also cloned and the deduced amino acid sequence showed that IL-6 receptor belongs to immunoglobulin superfamily. A second polypeptide chain involved for IL-6 signal transduction was also identified. The cDNA for lymphocyte Fcepsilon receptor (FcepsilonRII) was cloned. The sequence showed that FcepsilonRII had an unique structure, its C-terminus outside and N-terminal half of the molecule was shown to secrete as IgE binding factor and to be involved in the regulation of allergic reactions. FcepsilonRII was found to be identical with a B cell specific differentiation antigen, CD23. The presence of two different species of FcepsilonRII which were generated by differential RNA splicing mechanism and by the usage of different transcription initiation sites, was demonstrated. They were shown to be different in their intracytoplasmic portion and their expression was differently regulated.
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