Analysis of immature B cell activation and differentiation

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 07457088
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: KUMAMOTO 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
• Keywords: pre-B cell / rapamycin / phosphatase / MB-1 / signal transduction / 増殖 / 免疫抑制剤 / PP2A

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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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