| Project/Area Number |
03670183
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Juntendo University School of Medicine |
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Principal Investigator |
HIROSE Sachiko Juntendo Univ.School of Med. Associate Prof., 医学部, 助教授 (00127127)
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| Co-Investigator(Kenkyū-buntansha) |
WAKIYA Midori Juntendo Univ.School of Med. Associate Prof., 医学部, 助手 (00220848)
UEDA Genjiroh Juntendo Univ.School of Med. Associate Prof., 医学部, 助手 (90203439)
徳重 克年 順天堂大学, 医学部, 助手 (60188729)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | anti-DNA antibodies / systemic lupus erythematosus / somatic mutation / immunoglobulin variable region / class-switch / clonal proliferation / New Zealand mice / CD5B細胞 / New Zealand マウス / 全身性エリテマト-デス / 免疫グロブリン遺伝子 / ハイブリド-マ |
|---|
| Research Abstract |
The production of anti-DNA antibodies in SLE-prone NZB/W F1 mice show an age-associated IgM to IgG isotype-switching. A majority of IgM anti-DNA antibodies reported so far were shown to be germline-encoded, with no, if any, somatic mutation in the immunoglobulin variable (V) region. In contrast, IgG anti-DNA antibodies show somatic mutations in V regions, and B cells responsible for these antibody production are clonally selected and expanded. These findings suggest that while IgM anti-DNA antibodies are the product of antigen-nonspecific B cell activation, IgG anti-DNA antibodies are produced by antigen-specific mechanism.
In the present studies on examining IgM and IgG anti-DNA monoclonal antibodies derived from individual NZB/W F1 mice, we first demonstrate that IgM anti-DNA antibodies are also clonally selected and expanded and that somatic mutations in V regions are introduced before IgM to IgG isotype-switching. These somatic mutations are associated with the increase in DNA-binding activities, suggesting that, in contrast to the previous speculation, IgM anti-DNA antibodies are also produced by antigen-specific mechanism as in the case of IgG anti-DNA antibodies.
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