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Implication of B cell superantigen for pathogenesis of RA

Research Project

Project/Area Number 09670493
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionTokyo 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)
KeywordsB 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)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] 箱田雅之: "B細胞スーパー抗原" リウマチ. 37. 619-623 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masayuki Hakoda.: "Creneration and molecular characterization of monoclonal IgCr4 rheumatoid factor from a patient with rheumatoid arthritrs" Arn.Rheam.Dis.56. 74-77 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masayuki Hakoda: "Somatic mutations in immunoglobulin variable region genes encoding reactivity to staphy lococcal-proteinA in B cells" Arthritis Rheum.40(abstract). S245 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masayuki Hakoda: "Pathogenic implication of B cell saperantiger in rheumatoid arthritis" Arthritis Rheum.41(abstract). S163 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masayuki Hakoda: "B cell superantigen" Rheumachi. Vol 37. 619-623 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hakoda, M,et al.: "Generation and molecular characterization of monoclonal IgG4 rheumatoid factor from a patient with rheumatoid arthritis" Ann Rheum Dis. Vol 56. 74-77 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hakoda, M,et al.: "Somatic mutations in immunoglobulin variable region genes encoding reactivity to staphylococcal protein A in B cells from rheumatoid synovial tissues. (Abstract)" Arthritis Rheum. Vol 40, S245. (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hakoda, M,et al.: "Pathogenic implication of B cell superantigen in rheumatoid arthritis (Abstract)" Arthritis Rheum. Vol 41, S163. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hakoda,M.,et al: "Pathogenic implication of B cell superantigen in reumatoid arthritis" Arthritis & Rheumutism. 41・9. S163 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masayuki Hakoda: "Somatic mutations in immunoglobulin variable region genes encoding reactivity to staphylococcul protein A in B cells from rheumatoid synovial tissues.nmunobecds/particles." Arthvitis and Rhenmatism. 40・9. S245 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 箱田雅之: "B細胞スーパー抗原" リウマチ. 37・4. 619-623 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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