| Project/Area Number |
12470116
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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 Noboru St. Marianna University School of Medicine, Department of Immunology, Professor, 医学部, 助教授 (40235982)
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| Co-Investigator(Kenkyū-buntansha) |
永渕 裕子 聖マリアンナ医科大学, 難病治療研究センター, 助手 (80278001)
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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 |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2001: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2000: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | SLE / RAG / anti-DNA antibody / B lymphocytes / Receptor editing / apoptosis / 抗DNA抗体 / B細胞株 / EBウイルス / 抗CD40抗体 |
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| Research Abstract |
We have investigated expression of recombination activating gene (RAG) proteins by peripheral blood mature B lymphocytes of normal subjects and patients with SLE. Although normal B cells did not express RAG proteins spontaneously, activated B cells expressed RAGs. Recombination signal sequence (RSS) binding activity of the RAGs was verified by a gel shift assay. Usage of a most downstream Jκ, Jκ5, was evident in activated B cells expressing RAGs. λ chain and intracellular RAGs were simultaneously expressed on the purified κ+ B cells after activation. Both findings suggest secondary light chain rearrangement in mature B cells. Some of RAG-expressing B cells could have failed in productive secondary rearrangement and they died via apoptosis. Thus, RAG-expressing B cells would revise their surface Ig or would die, leading to elimination of the autoreactive B cells.
We found that anti-DNA autoAb secreting B cells in patients with SLE failed to express RAG spontaneously nor even with activation. Thus anti-DNA secreting B cells did not revise their Ig gene nor die via apoptosis, causing them to develop and persist autoAb secretion by SLE B cells. These results suggest that failure of RAG reexpression in anti-DNA secreting B cells may be important for autoAb production of SLE patients.
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