Implication of B cell superantigen for pathogenesis of RA
| Project/Area Number |
09670493
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | Tokyo Women's Medical University |
|---|
Principal Investigator |
HAKODA Masayuki Institute of Rheumatolog, Tokyo Women's Medical University, 医学部, 講師 (70208429)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
|---|
| Keywords | B cell / superantigen / rheumatoid arthritis / イムノグロブリン遺伝子 / VH3ファミリー / 細菌感染 / 慢性間接リウマチ / プロテインA / 黄色ブドウ球菌 / 感染症 |
|---|
| 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.
|
Report
(3 results)
Research Products
(11 results)
