| Project/Area Number |
10670310
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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 |
Immunology
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| Research Institution | Juntendo University |
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Principal Investigator |
HIROSE Sachiko Juntendo University, Dept.of Pathol., Associate Prof., 医学部, 助教授 (00127127)
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| Co-Investigator(Kenkyū-buntansha) |
張 丹青 順天堂大学, 医学部, 助手 (40296877)
ZHANG Danqing Juntendo University, Dept.of Pathol., Instructor
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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 |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | SLE / Natural antibody / IgG anti-DNA antibody / autoantibody / somatic mutation / Ig variable region gene / affinity selection / CAT gene / 抗体可変領域遺伝子 |
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| Research Abstract |
The production of pathogenic IgG autoantibodies is a hallmark of systemic lupus erythematosus (SLE). Studies on immuoglobulin variable region (IgV) gene sequences and DNA-binding activities of IgM and IgG anti-DNA monoclonal antibodies from SLE-prone (NZB x NZW) Fl mice showed that, in the process of IgM to IgG isotype switching, IgG anti-DNA antibodies are clonally selected, somatically mutated, and have a high-affinity nature. In contrast, IgM counterpart antibodies have poly-reactive and low-affinity nature and little if any somatic mutation in their IgV genes. These IgM anti-DNA antibodies are observed even in normal individuals and derived from B 1 cells normally functioning in natural immunity. Highly mutated pathogenic IgG anti-DNA antibodies are only observed in patients with SLE. To understand the mechanism of production of these pathogenic autoantibodies, we tried to establish chloramphenicil acetyl transferase (CAT) gene-transgenic SLE-prone mouse strains. CAT gene are inserted between IgH promoter region and intron enhancer, thus, in mice introduced with these CAT gene, transgene are expressed only in B cell lineages. Since CAT transgene is shown to be mutated in parallel with IgV, CAT transgene mutation will be a good marker for IgV mutation. There are many kinds of IgV in genomes and germ-line sequences are not available in many cases. Our mice will be useful to understand the mechanism of pathogenic mutated IgG autoantibody production in patents with SLE.
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