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Differentiation-induction of antibody producing human B cells from cord blood CD34+ cells in mice for generating monoclonal antibody used in clinical therapy

Research Project

Project/Area Number 12557032
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Immunology
Research InstitutionTokai University

Principal Investigator

HABU Sonoko  Tokai University, School of Medicine, Professor, 医学部, 教授 (30051618)

Co-Investigator(Kenkyū-buntansha) AZUMA Takachika  Tokyo University of Science, research Institute for Biological Science, Executive Director, 生命科学研究所・生命情報科学研究部門, 教授 (00028234)
IHARA Seiji  Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (50096202)
ANDOU Kiyoshi  Tokai University, School of Medicine, Assistant Professor, 医学部, 講師 (70176014)
TAKI Takao  Otsuka pharmaceutical co., ltd., Molecular Medial Science Institute, Executive Director, 所長 (10046295)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2001: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2000: ¥8,300,000 (Direct Cost: ¥8,300,000)
Keywordshuman immune system / T cell development / thymic environment / NOG mice / mice / B1 B cell / antiboy production / B cell development / B_1 B Cells / ヒト免疫系再構築 / モノクローナル抗体 / ヒト臍帯血 / オリゴクローン法
Research Abstract

Monoclonal antibodies are known to be useful as the clinical therapy from various animal models. However, therapeutic antibodies derived human B cells have not used in the clinical field although human/mouse chimera antibodies are available. In order to obtain monoclonal antibodies produced by human B cells, we tried to reconstitute human immune system in the immuno-deficient mice from CD34+ cells in cord blood (CB) in this study. We obtained the following results. 1) Human CD34+ cells develop into mature T cells with cytokine producing ability in the in vivo RTOC in which mouse thymic epithelial cells are reaggregated with human CD34+cells. 2) NOG mice are useful to reconstitute T cell development in vivo probably because they lack completely NK cell activity as well as T and B cells. 3) In vivo treatment of anti-CD40 antibody induces the increase of antigen specific antibody although IgG class is low. 4) CB CD34+ cells injected into NOG mice mainly develop into CD5+B cells in the spleen. 5) Using chimera anti-erbB-2 antibody and serum from malaria patients, antigen epitopes were identified. These peptides are going to use for immunizing NOG mice receiving DBCD34+ cells.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Atsushi Kumanogoh: "Increased T cell autoreactivety in the absence of CD40-CD40 ligand interactions : A role of CD4O in regulatory T cell development"J. Immunol.. 166. 353-360 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Keitarou Hayashi: "Overexpression of AML1 transcription factor drives thymocytes into the CD8 single-positive lineage"The Journal of Immunology. 167. 4957-4965 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takehiko Sato: "Surface molecules essential for positive selection are retained but Interferod in thymic epithelial cells after monolayer culture"Cellular Immunology. 211. 71-79 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Makoto Senoo: "Limited effect of chromatin remodeling on D β-to-JB β recombination in CD4^+CD8^+ thymocyte : Implications for a new aspect in the regulation of TOR β gene recombination"International Immunology. 13. 1405-1414 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] keitaro Hayashi: "Diminution of the AML1 transcription factor function causes differential effects on the fates of CD4 and CD8 single-positive T cells"J. Immunol. 165. 6816-6824 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinya Nagafuchi: "Dietary nucleotides can up-regulate antigen-specific Th 1 immune responses and suppress antigen-specific IgE responsesin mice"Int Arch Allergy Immunol. 122. 33-41 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satoshi Nunomura: "Molecular basis for functional maturation of thymocytes : Increase in c-fos translation with positive selection"The Journal of Immunology. 164. 5590-5595 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kan Shida: "Serum IgE response to orally ingested antigen : A novel IgE response model with allergen-specific T-cell receptor transgenic mice"J. Allergy Clin. Immunol. 105. 788-795 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wataru Ise: "Primary response of naitive CD4+ T cells to amino acid-substited analogs of an antigenic peptide can show distinct activation patterns : Th1-and Th2-type cytokine secretion, and helper activity for antibody production without apparent cytoki secretion"FEBS Letters. 465. 28-33 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsuto Hozumi: "Estblishment of efficient teaggregation culture system for gene transfection into imamture t cells by retroviral vectors"Immunol. Lett.. 71. 61-66 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 餅田尚子, 垣生園子: "免疫Immunology Frontier"メディカルレビュー社. 6 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 佐藤健人, 赤塚明, 垣生園子: "細胞培養工学"ニューサイエンス社. 5 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Atsushi Komanogoh, Sonoko Habu et, al: "Increased T cell autoreactivety in the absence of CD40-CD40 ligand interactions:A role of CD40 in regulatory T cell development"J.Immunol. 166. 353-360 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takehito Satou, Sonoko Habu et,al: "Surface molecules essential for positive selection are retained but Interfered in thymic epithelial cells after monolayer culture"Cellular Immunology. 211. 71-79 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Keitaro Hayashi, Natsumi Abe, Sonoko Habu et, al: "Overexpression of AML1 Transcription factor Drives Thymocytes intothe CD8 Single-Positive Lineage"J.Immunol. 167. 4957-4965 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Makoto Senoo, Naoko, Mochida, Sonoko Habu et, al: "Limited effect of chromatin remodeling on D β-to-Jbβrecombination in CD4* CD8* thymocyte : Implications for a new aspect in the regulation of TCRβ gene recombination"International Immunology. 13. 1405-1414 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinya Nagafuchi, Satoshi Hachimura, Sonoko Habu et, al: "Dietary mucleotides can up-regulate antigen-specific Th 1 immune responses and suppress antigen-specifid IgE responsesin mice"Int, Arch Allergy Immunol. 122. 33-41 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satoshi Nunomura, Takehito Sato, Sonoko Habu et, al: "Molecular basis for functional maturation of thymocytes: Increase in c-fos translation with positive selection"The Journal of Immunology. 164. 5590-5595 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Keitaro Hayashi, Waka Natsume, Sonoko Habu, et, al: "Diminution of the AML1 transceiption factor function causes differentiale effects on the fates of CD4 and CD8 single-positive T cells"The Journal of Immunology. 165. 6816-6824 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kan Shida, Satoshi Hachimura, Sonoko Habu, et, al: "Serum IgE response to orally ingested antigen: A novel IgE response model with allergen-specific T-cell receptor transgenic mice"J.Allergy Clin.Immunol. 105. 788-795 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wataru Ise, Mamoru Totsuka, Sonoko Habu et,al: "Primary response of native CD4 + T cells to amino acid-substited analogs of an antigenic peptide can show distinct activation patterns: Th1-and Th2-tyape cytokine secretion, and helper activity for antibody production without apparent cytoki secretion."FEBS Letters. 465. 28-33 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katuto Hozumi, Ryo Ohtsuka, Sonoko Habu et, al: "Establishment of efficient teaggregation culture system for gene transfection into imamture T cells bu retroviral vectors."Immunol. Left. 71. 61-66 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Naoko amochida and Sonoko Habu: "Inolvement of TRAIL in negative selection"Immunology Frontier. 11. 20-25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takehito Sato, Akira Akatsuka and Sonoko Habu: "Reaggregate thymic organ culture and T cell selection"THE TISSUE CULTURE ENGINEERING. 26. 9-13 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Atsushi Kumanogoh: "Increased T cell autoreactivety in the absence of CD40-CD40 ligand interactions:A role of CD40 in regulatory T cell development"J.Immunol.. 166. 353-360 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Keitarou Hayashi: "Overexpression of AML1 transcription factor drives thymocytes into the CD8 single-positive lineage"The Journal of Immunology. 167. 4957-4965 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takehiko Sato: "Surface molecules essential for positive selection are retained but Interferod in thymic epithelial cells after monolayer culture"Cellular Immunology. 211. 71-79 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Makoto Senoo: "Limited effect of chromatin remodeling on D β-to-JB β recombination in CD4^+CD8^+ thymocyte:Implications for a new aspect in the regulation of TCR β gene recombination"International Immunology. 13. 1405-1414 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 餅田尚子, 垣生園子: "免疫Immunology Frontier"メディカルレビュー社. 6 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Atsushi Kumanogoh,: "Increased T cell autoreactivety in the absence of CD40-CD40 ligand interactions : A role of CD40 in regulatory T cell development"Journal of Immunology. 166. 353-360 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoichi Matsunaga,: "Oral immunization with size-purified microsphere beads as a vehicle selestively induces systemic tolerance sensitization"Vaccine. 19. 579-588 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Keitaro Hayashi: "Diminution of the AML1 transcription factor function causes differential effects on the fates of CD4 and CD8 single-positive T cells"Journal of Immunology. 165. 6816-6824 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Satoshi Nunomura: "Molecular Basis for Functional Maturation of Thymocytes : Increase in c-fos Translation with Positive Selection."Journal of Immunology. 164. 5590-5595 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wataru Ise: "Primary response of naitive CD4+ T cells to amino acid-substited analogs of an antigenic peptide can show distinct activation patterns : Th1, and Th2, type cytokine secretion and helper activity for antibody production without apparent cytokine secretion."FEBS Letters. 465. 28-33 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Katsuto Hozumi: "Estblishment of efficient teaggregation culture system for gene transfection into imamture t cells by retroviral vectors."Immunol.Lett.. 71. 61-66 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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