1998 Fiscal Year Final Research Report Summary
Implication of B cell superantigen for pathogenesis of RA
| Project/Area Number |
09670493
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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 |
内科学一般
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
HAKODA Masayuki Institute of Rheumatolog, Tokyo Women's Medical University, 医学部, 講師 (70208429)
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| Project Period (FY) |
1997 – 1998
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| Keywords | B cell / superantigen / rheumatoid arthritis |
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| Research Abstract |
Several microbial and endogenous proteins bind to immunoglobulins expressing specific VH families independent on the usage of D, JH and light chain genes. Among these candidate B cell superantigens, staphylococcal protein A (SPA) has been characterized in most detail. SPA binds to Igs expressing VH3 genes and preferentially stimulates IgM B cells expressing VH3 genes. To investigate whether there is any pathogenic relevance of B cell superantigens to inflammatory diseases, SPA-binding IgM B cell repertoire was examined in the peripheral blood of patients with rheumatoid arthritis (RA). The frequency of B cells committed to the production of SPA-binding IgM was higher in RA blood as compared to normal blood. We previously reported that the SPA-binding IgM from normal blood was divided into two groups based on the differential binding avidities for solid-phase SPA and that the differential binding avidities for SPA were derived from specific germ-line VH3 gene usage. The increase in B cells with SPA-binding IgM in RA blood was largely due to the increase in IgM B cells with high avidities for SPA.The nucleotide sequence analysis of the expressed heavy chain genes in randomly-selected 35 B cell clones producing SPA-binding IgM from RA blood confirmed that the high avidities of IgM for SPA were dependent on the usage of specific germ-line VH3 genes, but not the results from somatic mutational events. To investigate the biological significance of germ-line VH3 gene-encoded differential binding avidities for SPA, phylogenetic analysis of the functional germ-line VH3 sequences was performed. The result suggested that the germ-line VH3 genes encoding low avidities for SPA diverged from the genes encoding high avidities for SPA.Our results implicate that B cell superantigens may provide unique models for the investigatigation of the interrelationships among infection, immune diversification, and development of autoimmune diseases.
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