2001 Fiscal Year Final Research Report Summary
Analysis of RAG expression in antibody-secreting B cell of SLE patients
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 |
Section | 一般 |
Research Field |
内科学一般
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Research Institution | St. Marianna University School of Medicine |
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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Project Period (FY) |
2000 – 2001
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Keywords | SLE / RAG / anti-DNA antibody / B lymphocytes / Receptor editing / apoptosis |
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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[Publications] Takeba Y, Nagafuchi H, Takeno M, Kasiwakura J, Suzuki N, Takeba Y, Nagafuchi H, Takeno M, Kasiwakura J, Suzuki N: "Txk, amember of non-receptor tyrosine kinase of Tec family acts as a Th1 cell specific transcription factor and regulates IFN-gamma gene transcription"J Immunol. 168・5. 2365-2183 (2002)
Description
「研究成果報告書概要(和文)」より
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