2000 Fiscal Year Final Research Report Summary
What is the antigen that induce myasthenia gravis? : the specificity of anti-AchR antibody in the patient of myasthenia gravis
Project/Area Number |
11671335
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Thoracic surgery
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Research Institution | NAGOYA CITY UNIVERSITY |
Principal Investigator |
YAMAKAWA Yosuke Nagoya City University, Medical School, Associate Professor, 医学部, 助教授 (40148284)
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Co-Investigator(Kenkyū-buntansha) |
FUJII Yoshitaka Nagoya City University, Medical School, Professor, 医学部, 教授 (40156831)
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Project Period (FY) |
1999 – 2000
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Keywords | apoptosis / thymocytes / germinal center B cells / Bcl-2 / Bcl-x / Bax / Bak / Bim |
Research Abstract |
Myasthenia gravis is auto-immune disease because of anti-AchR antibody. It is said that auto-immune disease is interacted with auto-reactive T cell. Auto-reactive T cell must be deleted with apoptosis in T cell development. Bcl-2 family proteins regulate programmed cell death, and may play an important role in the selection of lymphocytes. We investigated the expression of Bcl-2, Bcl-x, Bax, Bak and Bim in human lymphocytes using flow-cytometry. Bcl-2 was down-regulated in CD4^+8^+ (DP) thymocytes and CD19^+38^+ tonsillar lymphocytes (GC B cells). Among DP thymocytes, cells co-expressing CD69 up-regulated Bcl-2, suggesting that the role of Bcl-2 is promoting survival of positively selected DP cells. Unexpectedly, the expression level of Bcl-x was higher in DP cells than in Single Positive (SP) cells and in CD69^+ DP thymocytes it was lower than in CD69^- DP thymocytes. Expression of Bim was low in DP thymocytes but high in a subset of GCB cells. Bim and Bax were expressed more highly in SP than in DP thymocytes. Among peripheral blood lymphocytes (PBL), CD8^+ T cells expressed a〜10 fold higher level of Bcl-x than CD4^+ T cells while both subsets expressed similar levels of Bcl-2. Bak expression was low and Bim expression was absent in PBL.These results suggest that not only Bcl-2 but other members of the Bcl-2 family are involved in T cell development in the thymus and affinity maturation of B cells in the germinal center
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