Regulatory Mechanisms of Antibody Class Expression and Therapy of Autoimmunity
| Project/Area Number |
01570184
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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 | Tokyo Metropolitan Institute for Neurosciences |
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Principal Investigator |
YAKURA Hidetaka Tokyo Metropolitan Institute for Neurosciences, Member, 微生物学, 副参事 (60166486)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Kazuya Tokyo Metropolitan Institute for Neurosciences, Staff Scientist, 微生物学, 主任研究員 (00219643)
OGIMOTO Mami Tokyo Metropolitan Institute for Neurosciences, Staff Scientist, 微生物学, 主事研究員 (80158609)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Autoimmunity / Antibody Class Switch / Protein Tyrosine Phosphatase / CD45 / Lyb-2 / IL-4 / 抗体クラス / Lyー5(CD45) / 自己免疫 / モノクロ-ナル抗体による治療 |
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| Research Abstract |
We have demonstrated that CD45 selectively regulates the commitment step to all the IgG subclass producers, and Lyb-2 regulates IgG1 production induced by IL-4 in LPS-activated B cells by acting also on the generative step of IgG1 precursor cells. The present project was conducted to examine the molecular mechanisms whereby CD45 and Lyb-2 control IgG synthesis in B cells activated by LPS and IL-4 and to see whether autoimmune pathology caused by the abnormality in antibody class switching can be alleviated by modulating IgG production.
Northern blot analysis showed that steady-state levels of C_<gamma>3, C_<gamma>2b and C_<gamma>1, but not C_<mu>, mRNA in LPS-activated B cells were reduced about 2-to 5-fold by CD45 mAb and that C_<gamma>1 mRNA level in B cells activated by LPS and IL-4 was significantly decreased by Lyb-2 mAb and CD45 mAb. Further, expression of germline _<gamma>1 transcripts induced by IL-4 and of germline _<gamma>2b and _<gamma>3 transcripts induced by LPS was inhibited by Lyb-2 mAb and CD45 mAb, respectively. These results suggest that the signals delivered through CD45 and Lyb-2 differentially regulate processes of germline C_H gene expression prior to class switch recombination.
To study physiological functions of CD45 and to evaluate relevance of CD45 in clinical settings, we selected one of the systemic lupus erythematosus-prone mice, BXSB, as a model.
The BXSB disease features polyclonal B cell activation, autoantibodies to double-stranded DNA and fatal glomerulonephritis, and there is a progressive switch from IgG to IgG that evidently coincides with onset of autoimmune pathology. We therefore investigated whether the development of autoimmunitycan be prevented by reducing IgG antibody production with administration of CD45 mAb. The results indicate that some forms of autoimmune disease can be effectively treated by reducting the concentration of IgG autoantibody with CD45 mAb.
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Report
(3 results)
Research Products
(13 results)
