| Project/Area Number |
11670451
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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 |
内科学一般
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| Research Institution | Saga Medical School |
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Principal Investigator |
NAGASAWA Kohei Saga Medical School, Internal Modicine, Professor, 医学部, 教授 (00108721)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAKE Kensuke Saga Medical School, Immunology, Associate professor, 医学部, 助教授 (60229812)
TADA Yoshifumi Saga Medical School, Internal Medicine, Instructor, 医学部, 助手 (70284627)
KOARADA Syuichi Saga Medical School, Internal Medicine, Instructor, 医学部, 助手 (50304887)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | B cell / RP105 / SLE / Sjogren's syndrome / Dermatomyositis / Apoptosis / Anti-DNA antibody / IgG / 免疫グロブリン / 自己抗体 / 活性化B細胞 / ステロイド / apoptosis |
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| Research Abstract |
PR105, a novel molecule expressed on B cells, has been described to be associated with B cell proliferation or apoptpsis in mice. As the knowledge of its function in humans, however, was very limited, we attemted to analyze its expression and function in B cells in systemic autoimmune diseases. As in mice, virtually all B cells in the peripheral blood of normal subjects expressed the RP105 molecule. Interestingly, however, the proportion of B cells lacking RP105 was increased to 15.9%, 14.5% and 20.2% in systemic lupus erythematosus(SLE), Sjogren's syndrome(SjS) and dermatomyositis(DM), respectively. The phenotypic analysis indentified RP105-negative B cells as highly activated and well differetiated B cells. It was also found that the number of RP105-negative B cells changed in pararell with the disease activity of SLE.
In patients with SjS, histological examination of salivary gland revealed that the inflammatory lesions mainly consisted of RP105-negative B cells and that the rate of those cells were well correlated with the serum concentration of IgG.Large percentage of RP105-negative B cells in the peripheral blood in DM patients was a striking contrast to small number of those cells in patients with polymyositis(PW), indicating the immunological difference of DM from PM.
In vitro experiments showed that RP105-negative B cells were more susceptible to corticosteroid-induced apoptosis than positive B cells. Moreover, it was of great interest that RP105-negative B cells produced significant amount of anti-DNA antibodies as well as nonspecific IgG whereas positive B cells did not even with any stimulation.
Taken together, RP-105 negative B cells may play an important role in the pathogenesis of certain autoimmune diseases in which antibody-mediated immune mechanisms are involved.
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