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Analysis of immature B cell activation and differentiation

Research Project

Project/Area Number 07457088
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKUMAMOTO UNIVERSITY (1996-1997)
Tottori University (1995)

Principal Investigator

SAKAGUCHI Nobuo  Kumamoto University, School of Medicine, Professor, 医学部, 教授 (70192086)

Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥3,100,000 (Direct Cost: ¥3,100,000)
Keywordspre-B cell / rapamycin / phosphatase / MB-1 / signal transduction / 増殖 / 免疫抑制剤 / PP2A / 抗原レセプター / Igα(MB-1) / α4 / ホスファターゼ / 細胞周期 / 細胞増殖 / pre-B細胞 / 細胞分化 / 胎児
Research Abstract

To study the activation and development of immature B lineage cells, we searched the unique signal transduction molecules expressed in the immature B cells or in the process of B cell activation.
We characterized the pre-BCR signal transduction molecules, among which PI-3 kinase activity was shown to be involved in the pre-B cell stages. We also isolated a molecule named immunoglobulin-receptor binding protein (IGBP-1/alpha4) , which is originally identified as a phosphoprotein co-precipitated with the BCR-component MB-1 molecule. The alpha4 gene was isolated and characterized. The recent results also showed that the alpha4 protein is associated with the protein phosphatase 2 A,whose association is critical for the proliferation of B cells. The alpha4/PP2A complex is shown to be a novel target of rapamycin. These results implicated the novel signal transduction pathway involved in the proliferation of lymphoid cells.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Igarashi H.: "Telomerase activity is induced in human peripheral B lymphocytes by the stimulation to antigen receptor." Blood. 89. 1229-1307 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mitsuyoshi S.: "Expression of the proliferation-related Ki-67 mRNA in the early development of murine embryo." Biochemical Biophysical Research Communication. 235. 191-196 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsuo Y.: "A novel ALL-L3 cell line,BALM-16,lacking expression of immunoglobulin chains derived from a patient with hypercalcemia." Leukemia. 11. 2168-2174 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Onda M.: "Expression and chromosomal localization of the human α4 gene whose structure is closely related to the yeast TAP42 protein of rapamycin-sensitive signal transduction pathway." Genomics. 46. 373-378 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Baba M.: "Mouse germinal center B cells with the xid mutation retain responsiveness to anti-mouse CD40 antibodies but diminish IL-5 responsiveness." International Immunology. 9. 1463-1473 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamanouchi S.: "Stimulation to T cell differentiation antigen Ly6C inhibits proliferation of T cells by inhibiting the secretion of IL-2 from CD4 positive T cells." European Journal Immunology. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hideya Igarashi and Nobuo Sakaguchi.: "Telomerase activity is induced in human peripheral B lymphocytes by the stimulation to antigen receptor." Blood. 89. 1229-1307 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Saori Mitsuyoshi, Hideya Igarashi, Atsuko Sakata, Akihiko Koseki, Masaru Taniguchi, and Nobuo Sakaguchi.: "Expression of the proliferation-related Ki-67 mRNA in the early development of murine embryo." Biochemical Biophysical Research Communication. 235. 191-196 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshinobu Matsuo, Roderick AF MacLeod, Hans G.Drexler, Kensuke Kojima, Kazuhiko Kuwahara, Chiharu Nishizaki, Shunichi Fukuda, Yuko Inoue, Tatsuo Sezaki, Nobuo Sakaguchi, and Kunzo Orita.: "A novel ALL-L3 cell line, BALM-16, lacking expression of immunoglobulin chains derived from a patient with hypercalcemia." Leukemia. 11. 2168-2174 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mitsugi Onda, Seiji Inui, Kazuhiko Maeda, Mikio Suzuki, Ei-ichi Takahashi and Nobuo Sakaguchi.: "Expression and chromosomal localization of the human alpha4 gene whose structure is closely related to the yeast TAP42 protein of rapamycin-sensitive signal transduction pathway." Genomics. 46. 373-378 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masashi Baba, Yuji Kikuchi, Shigeo Mori, Hiroshi Kimoto, Seiji Inui, Nobuo Sakaguchi, Jun-ichiro Inoue, Tadashi Yamamoto, Toshitada Takemori, Maureen Howard and Kiyoshi Takatsu.: "Mouse germinal center B cells with the xid mutation retain responsiveness to anti-mouse CD antibodies but diminish IL-5 responsiveness." International Immunology. 9. 1463-1473 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sachiko Yamanouchi, Kazuhiko Kuwahara, Atsuko Sakata, Taichi Ezaki, and Nobuo Sakaguchi.: "Stimulation to T cell differentiation antigen Ly6C inhibits proliferation of T cells by inhibiting the secretion of IL-2 from CD4 positive T cells." European Journal Immunology. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Seiji Inui, Atsuko Sakata, Kazuhiko Maeda, Junichi Miyazaki, and Nobuo Sakaguchi.: "Introduction of human CD40 gene with immunoglobulin enhancer and promoter creates mice with a population of human CD40^+ early B lineage cells in the bone marrow." Transgenics. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazuhiko Maeda, Seiji Inui, Hideki Sanjo, and Nobuo Sakaguchi.: "The gene structure and promoter analysis of mouse lymphocyte signal transductionmolecule alpha4 that is involved in a rapamycin-sensitive pathway." Gene. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Igarashi H.: "Telomerase activity is induced in human peripheral B lymphocytes by the stimulation to antigen receptor." Blood. 89. 1229-1307 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mitsuyoshi S.: "Expression of the proliferation-related Ki-67 mRNA in the early development of murine embryo." Biochemical Biophysical Research Communication. 235. 191-196 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsuo Y.: "A novel ALL-L3 cell line, BALM-16, lacking expression of immunoglobulin chains derived from a patient with hypercalcemia." Leukemia. 11. 2168-2174 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Onda M.: "Expression and chromosomal localization of the human α4 gene whose structure is closely related to the yeast TAP42 protein of rapamycin-sensitive signal transduction pathway." Genomics. 46. 373-378 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Baba M.: "Mouse germinal center B cells with the xid mutation retain responsivenes to anti-mouse CD40 antibodies but diminish IL-5 responsiveness." International Immunology. 9. 1463-1473 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamanouchi S.: "Stimulation to T cell differentiation antigen Ly6C inhibits proliferation of T cells by inhibiting the secretion of IL-2 from CD4 positive T cells." European Journal Immunology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsuo Y.: "Four subclones with distinct immunoglobulin light chain phenotypes(χ^+λ^+,χ^+,λ^+and χ^-λ^-)from acute leukemia." Leukemia. 10. 700-706 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Igarashi H.: "Telomerase activity is induced by the stimulation antigen receptor in human periphera lymphocytes." Biochem.Biophys.Res.Commun.219. 649-655 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakanishi K.: "IL-4 and anti-CD40 protect against Fas-mediated B cell apoptosis and induce B cell growth and differentiation." Int.Immunol.8(5). 791-798 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kuwahara K.: "Cross-linking of B cell antigen receptor-related structure pre-B cell induces tyrosine phosphorylation of p85 and p110 subunits and activation of phosphatidylinositol 3-kinase." Int.Immunol.8(8). 1273-1285 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamashita Y.: "Activation mediated by RP105 but not CD40 makes normal B cells susceptible to anti-IgM-induced apoptosis : A role for Fc receptor co-ligation." J.Exp.Med.184. 113-120 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Igarashi H.: "Telomerase activity is induced in human peripheral B lymphocytes by the stimulation to antigen receptor." Blood. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Inui,S.: "Signal transduction through B cell specific molecule MB-1 in early lymphoid progenitor cells" Leucocyte Typing V. 673-674 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kataoka,S.: "Establishment of a monoclonal antibody which co-stimulates the proliferation of B lymphocytes in vitro" Yonago Acta medica. 38. 159-167 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nomura,J.: "Anti-CD40 monoclonal antibody induces the proliferation of murine B cells as a B cell mitogen through a distinct pathway from receptors for antigens or lipopolysaccharide" Immunology Letters. 45. 195-203 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Inui,S.: "Molecular cloning of a cDNA clone encoding a phosphoprotein component related to the immunogloblin receptor (IgR) -mediated signal transduction" J.Immunol.154. 2714-2723 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Igarashi,H.: "Telomerase activity is induced by the stimulation to antigen receptor in human peripheral lymphocytes" Biochem.Biophys.Res.Commun.(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsuo,Y.: "Four subclones with distinct immunoglobulin light chain phenotypes (κ^+λ^+,κ^+,λ^+ and κ^-λ^-) from acute leukemia" Leukemia. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakanishi,K: "IL-4 and anti-CD40 protect against Fas-mediated apoptosis and induce the proliferation and differentiation of anti-CD40-activated B cells" Int.Immunol.(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 阪口薫雄: "標準免疫学" 医学書院(印刷中), (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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