A study on the B cell clonality in autoimmune neurological disorders.

• Project/Area Number: 07807066
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Tokyo Women's Medical College
• Principal Investigator: HASHIMOTO Shiori Tokyo Women's Medical College, Assistant Professor, 医学部, 助手 (60180824)
• Project Period (FY): 1995 – 1996
• Project Status: Completed (Fiscal Year 1996)
• Budget Amount: ¥2,100,000 (Direct Cost: ¥2,100,000); Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: autoimmune disease / neurological disorder / immunoglobulin / apoptosis / 自己免疫性神経疾患 / B細胞クロナリティー / 免疫グロブリン遺伝子

Research Abstract

I have established a method to make human B cell lines from peripheral blood B cells, and to subsequently determine their nucleotide sequences of the immunoglobulin heavy chain gene by RTPCR.By analyzing the sequences of immunoglobulin genes of the rheumatoid factor-producing B cells from rheumatoid arthritis patients, I have clearly shown that substantial amounts of somatic mutations are introduced within the hypervariable regions, especilly CDR3 (complementary determining reqion 3), indicating that the antigen-driven mechanism would play an important role in the production of those autoantibodies. I have also shown that LDOPA and bucillamine, which have been successfully used for the treatment of parkinson's disease and rheumatoid arthritis, respectively, can induce apoptosis via the generation of reactive oxygen species (ROS), by demonstrating the inhibition of apoptosis by addition of anti-oxidants, such as superoxide dismutase and catalase, as well as by directly showing the increase of the intracellular amounts of ROS using flow cytometry.

Research Products

• [Publications] Jain.R.I.: "Ig H and L chain variable region gene sequence analyses of twelve synovial tissue-derived B cell lines producing IgA, IgG, and IgM rheumatoid factors structure/function comparisons of antigenic specificity, V gene sequence, and Ig isotype." Autoimmunity. 22. 229-243 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sawada T: "Generation of reactive oxygen specied is required for bucillamine, a novel anti-rheumatic drug, to induce apoptoshis in concert with copper." Immunopharmacology. 35. 195-202 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Jain.R.I., F.Fais, S.Kaplan, B.Sellars, R.Brooks, E.Chartash, R.Furie, S.Hashimoto, and N.Chorazzi: "Ig H and L chain variable region gene sequence analyzes of twelve synovial tissue-derived B cell lines producing IgA,IgG,and IgM rheumatoid factors structure/function comparisons of antigenic specificity, V gene sequence, and Ig isotype." Autoimmunity. 22. 229-243 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sawada T., Hashimoto S., Furukawa H., Tohma S., Inoue T.and K.Ito: "Generation of reactive oxygen species is required for bucillamine, a novel anti-rheumatic drug, to induce apoptosis in concert with copper." Immunopharmacology. 35. 195-202 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Jain.R.I.: "Ig H and L chain variable region gene sequence analyses of twelve synovial tissue-derived B cell lines producing IgA,IgG,and IgM rheumatoid factors structure/function comparisons of antigenic specificity,V gene sequence,and Ig isotype." Autoimmunity. 22. 229-243 (1995)
• [Publications] Sawada T: "Generation of reactive oxygen species is required for bucillamine,a novel anti-rheumatic drug,to induce apoptosis in concert with copper." Immunopharmacology. 35. 195-202 (1996)