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2001 Fiscal Year Final Research Report Summary

Analysis of RAG expression in antibody-secreting B cell of SLE patients

Research Project

Project/Area Number 12470116
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

SUZUKI Noboru  St. Marianna University School of Medicine, Department of Immunology, Professor, 医学部, 助教授 (40235982)

Project Period (FY) 2000 – 2001
KeywordsSLE / RAG / anti-DNA antibody / B lymphocytes / Receptor editing / apoptosis
Research Abstract

We have investigated expression of recombination activating gene (RAG) proteins by peripheral blood mature B lymphocytes of normal subjects and patients with SLE. Although normal B cells did not express RAG proteins spontaneously, activated B cells expressed RAGs. Recombination signal sequence (RSS) binding activity of the RAGs was verified by a gel shift assay. Usage of a most downstream Jκ, Jκ5, was evident in activated B cells expressing RAGs. λ chain and intracellular RAGs were simultaneously expressed on the purified κ+ B cells after activation. Both findings suggest secondary light chain rearrangement in mature B cells. Some of RAG-expressing B cells could have failed in productive secondary rearrangement and they died via apoptosis. Thus, RAG-expressing B cells would revise their surface Ig or would die, leading to elimination of the autoreactive B cells.
We found that anti-DNA autoAb secreting B cells in patients with SLE failed to express RAG spontaneously nor even with activation. Thus anti-DNA secreting B cells did not revise their Ig gene nor die via apoptosis, causing them to develop and persist autoAb secretion by SLE B cells. These results suggest that failure of RAG reexpression in anti-DNA secreting B cells may be important for autoAb production of SLE patients.

  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Takeba Y, Suzuki N, Wakisaka S, Takeno M, Kaneko A. Asai T, Sakane T: "Involvement of cAMP responsive element binding protein (CREB) in the synovial cell hyperfunction in patients with rheumatoid arthritis"Clin Exp Rheumatol. 18. 47-55 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wakisaka S, Suzuki N, Kaneko N, Asai T, Sakane T: "Characterization of tissue outgrowth developed in vitro in patients with rheumatoid arthritis ; involvement of T cells in the development of tissue outgrowth"Int Arch Allergy Immunol. 121. 68-79 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokoe T, Suzuki N, Minoguichi K, Adachi M, Sakane T: "Analysis of IL-12 receptor β2 chain expression of circulating T lymphocytes in patients with atopic asthma"Cell Immunol. 208. 34-42 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki N, Takeno M, Takeba Y, Miyagi T, Ye JM, Nagafuchi H, Sakane T: "Induction of differentiation of mouse embryonic stem (ES) cells in culture. I. Treatment with BMP-2 and BMP-4 induces chondrocyte differentiation"The St. Marianna Medical Journal. 29. 25-31 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeba Y, Suzuki N, Kaneko A, Asai A, Sakane T: "Endorphin and enkephalin ameliorate excessive synovial cell functions in patients with rheumatoid arthritis"J Rheumatol. 28・10. 2176-2183 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kasiwakura J, Suzuki N, Takeno M, Itoh S, Oku T, Sakane T, Nakajin S, Thyosima S: "Evidence of autophosphorylationin Txk : Y91 is autophosphorylation site"Biological & Pharmaceutical Bulletin. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeba Y, Nagafuchi H, Takeno M, Kasiwakura J, Suzuki N, Takeba Y, Nagafuchi H, Takeno M, Kasiwakura J, Suzuki N: "Txk, amember of non-receptor tyrosine kinase of Tec family acts as a Th1 cell specific transcription factor and regulates IFN-gamma gene transcription"J Immunol. 168・5. 2365-2183 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mihara S, Suzuki N, Takeba Y, Soejima K, Yamamoto Y: "Combination of molecular mimicry and aberrant autoantigen expression is important for development of anti-Fas Jigand autoantibodies in patients with SLE"Clin Exp Immunol. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 坂根剛, 鈴木登: "全身性エリテマトーデスにおける自己抗体産生の分子免疫学的機序"日本臨床免疫学会雑誌. 23. 499-504 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 下山義博, 岳野光洋, 永渕裕子, 鈴木登, 坂根剛: "ベーチェット病患者好中球における自発的なサイトカイン産生"炎症. 20. 157-164 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高井憲治, 小川賢一, 岳野光洋, 鈴木登, 坂根剛: "聖マリアンナ医科大学免疫学・病害動物学教室において過去8年間に経験した寄生虫・衛生動物疾患の検討"聖マリアンナ医科大学雑誌. 29. 15-20 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 橋本博史, 吉木敬, 鈴木和男, 徳永勝士, 有村義宏他: "厚生労働省厚生科学特定疾患・難治性血管炎に関する調査研究報告"日本臨床免疫学会誌. 24. 336-346 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakane T, Suzuki N: "Neuro-endocrine-immune axis in human rheumatoid arthritis"Archivum Immunologiae et Therapiae Experimentalis. 48. 417-427 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登: "特殊型重症べーチェット病の治療"今月の治療. 8. 533-535 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 星野孝, 坂根剛, 鈴木登, 玉木京子: "神経・内分泌・免疫系の変動よりみた癌免疫療法-現状と将来"癌治療と宿主. 12. 350-362 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武半優子, 鈴木登: "神経ペプチドによる炎症の制御"臨床免疫. 35. 314-319 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登: "医学と医療の最前線.膠原病と神経・内分泌・免疫系の関わり"日本内科学会雑誌. 90. 153-161 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登: "膠原病における進歩と今後の展望:全身性エリテマトーデス患者自己抗体産生細胞のアポトーシス回避機構の解析とその是正"炎症・再生. 21・6. 635-638 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登: "ループス腎炎発症関連遺伝子とレセプターエディティング"炎症・再生. 21・5. 557-563 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登: "膠原病-診断治療の進歩Behcet病"医学のあゆみ. 199・5. 411-415 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登: "RAにおけるRAG発現異常"RA&セラピー. 7・4. 32-39 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登: "TxkによるTh1サイトカイン発現誘導"臨床免疫. 36・5. 687-693 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登, 武半優子: "オピオイドペプチドと関節炎"リウマチ科. 25・6. 523-527 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] Sakane T, Suzuki N, Takeno M: "Innate and acquired immunity in Beheet's disease. Beheet's Disease"D Bang, E-S Lee, and S Lee. 673 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki N: "The pathogenic role of prolactin in patients with rheumatoid arthritis. Neuroimmune Biology, vol.3"R Rapaport and L Matera(in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakane T, Suzuki N: "Neuro-endocrine-immune axis in human rheumatoid arthritis"Autoimmunity Kluwer Academic Publishers. 417-427 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakane T, Suzuki N: "Behcet's syndrome. The Molecular Pathology of Autoimmunity, Second Edition"A N Theofilopoulos and C A Bona(in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki N, Takeno M, Takeba Y, Nagafuchi H, Sakane T: "Autoimmunity in Behcet's disease. Immunnology of Behcet's disease"M Zierhut, S Ohno(in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeno M, Simoyama Y, Nagafuchi H, Suzuki N, Sakane T: "Neurophil hyperfinctionon Behcet's disease. Immunnology of Behcet's disease"Zierhut, S Ohno(in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登: "自己抗体産生Bリンパ球におけるRAG発現異常,自己抗体と自己免疫'00、第7回自己抗体と自己免疫シンポジウム講演録集"(株)医学生物学研究所. 31-38 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登, 坂根剛: "Th1細胞分化とTecファミリー非レセプター型細胞内チロシンキナーゼTxk, Annual Review免疫2001"中外医学社. 65-72 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登: "原発性免疫不全症候群,在宅介護のための難病ガイド"日本医学出版. 120-121 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登: "好酸球増多症候群,在宅介護のための難病ガイド"日本医学出版. 93-94 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 坂根剛, 岳野光洋, 鈴木登: "ベーチェット病,リウマチナビゲーター"メディカルレビュー. 198-199 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 坂根剛, 鈴木登: "修飾自己抗原,免疫学辞典 第2版"東京化学同人. 341 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 坂根剛, 鈴木登: "皮膚分化抗原,免疫学辞典 第2版"東京化学同人. 508 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 坂根剛, 鈴木登: "老衰細胞抗原,免疫学辞典 第2版"東京化学同人. 672 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木登: "免疫不全の分子機構,わかりやすい内科学第2版"文光堂. 310-313 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeba Y, Suzuki N, Wakisaka S, Takeno M, Kaneko A, Asai T, Sakane T: "Involvement of cAMP responsive element binding protein (CREB) in the synovial cell hyperfunction in patients with rheumatoid arthritis"Clin Exp Rheumatol. 18. 47-55 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wakisaka S, Suzuki N, Kaneko A, Asai T, Sakane T: "Characterization of tissue outgrowth developed in vitro in patients with rheumatoid arthritis ; involvement of T cells in the development of tissue outgrowth"Int Arch Allergy Immunol. 121. 68-79 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakane T, Suzuki N: "Possible correction of abnormal rheumatoid arthritis synovial cell function by jun D transfection in vitro [letter]"Arthritis Rheum. 43. 945-946 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakane T, Takeno M, Suzuki N: "Behcet's disease [letter]"N Engl J Med. 342. 588-589 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokoe T, Suzuki N, Minoguchi K, Adachi M, Sakane T: "Analysis of IL- 12 receptor β2 chain expression of circulating T lymphocytes in patients with atopic asthma"Cell Immunol. 208. 34-42 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki N, Takeno M, Takeba Y, Miyagi T, Ye JM, Nagafuchi H, Sakane T: "Induction of differentiation of mouse embryonic stem (ES) cells in culture. I. Treatment with BMP-2 and BMP-4 induces chondrocyte differentiation"The St. Marianna Medical Journal. 29. 25-31 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeba Y, Suzuki N, Kaneko A, Asai A, Sakane T: "Endorphin and enkephalin ameliorate excessive synovial cell functions in patients with rheumatoid arthritis"J Rheumatol. 28. 2176-2183 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kasiwakura J, Suzuki N, Takeno M, Itoh S, Oku T, Sakane T, Nakajin S, Toyosima S: "Evidence of autophosphorylation in Txk : Y91 is autophosphorylation site"Biological & Pharmaceutical Bulletin. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeba Y, Nagafuti H, Takeno M, Kasiwakura J, Suzuki N: "Txk, a member of non-receptor tyrosine kinase of Tec family, arts as a Th1 cell specific transcription factor and regulates IFN-gamma gene transcription"J. Immuol.. 168 (5). 2365-2370 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mihara S, Suzuki N, Takeba Y, Soejima K, Yamamoto Y: "Combination of molecular mimicry and aberrant autoantigen expression is important for development of anti-Fas ligand autoantibodies in patients with SLE"Clin. Exp. Immuol.. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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