| Project/Area Number |
10470127
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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 | 一般 |
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| Research Field |
内科学一般
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| Research Institution | ST,MARIANNA UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
SUZUKI Noburu ST.MARIANNA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENTS OF INNUNOLOG AND MEDICINE, SENIOR ASSOCIATE PROFESSOR, 医学部, 助教授 (40235982)
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| Co-Investigator(Kenkyū-buntansha) |
SAKANEI Tsuyoshi ST.MARIANNA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENTS OF INNUNOLOG AND MEDICINE, PROFESSOR, 医学部, 教授 (40127519)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 1999: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1998: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | RECEPTOR EDITING / RESOMBINATION / APOPTOSIS / SYSTEMIC LUPUS ERYTHEMATOSUS / RAG / AUTOANTIBODY / ANTI DNA ANTIBODY / recombnation |
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| Research Abstract |
Normal mature B lymphocytes have recently been shown to reexpress RAG proteins. The studies suggest a role of RAG reexpressed in mature B cells for their changing Ag receptor specificity in the further maturational process of mature B lymphocytes. Here, we have characterized RAG expression of mature B lymphocytes. Normal peripheral blood B cells did not express RAG proteins spontaneously. Activation by SAC+IL-2 and anti-CD40+IL-4, IL-7, or IL-10 induced cytoplasmic expression of RAGs. Nuclear translocation and recombination signal sequence binding activity of the RAG complex were verified by Western blotting and a gel shift assay. Usage of a downstream JィイD2kィエD2 was evident in B cells having expressed RAG complex. Λ light chain and intracellular RAGs were simultaneously expressed on the purified k+B cells after activation with SAC+IL-2 for 3-4 days, suggesting rearrangement of light chain gene in normal human mature B cells. Some of RAG expressing B cells, which may have resulted in unsuccessful secondary rearrangement died via apoptosis, evidenced by annexin V binding. If autoreactive B cells express RAGs appropriately, they would revise their surface immunoglobulin or would die, leading to elimination of the autoreactive B cells. We found that anti-DNA auto Ab secreting B cells did not express RAG at all, and thus the B cells secreting anti-DNA did not revise their lg gene nor die via apoptosis, allowing development and persistence of autoAb secretion in SLE patients. These results suggest that failure of RAG reexpression in anti-DNA secreting B lymphocytes may be important for the auotAb secretion of SLE patients.
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