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Study of Early b Cell Development

Research Project

Project/Area Number 02454193
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionKumamoto University

Principal Investigator

NISHIKAWA Shin-ichi  Kumamoto University Medical School, Institute for Medical Immunology, Professor., 医学部, 教授 (60127115)

Co-Investigator(Kenkyū-buntansha) HAYASHI Shin-ichi  Kumamoto University Medical School, Institute for Medical Immunology, Assistant, 医学部, 助手 (50208617)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1991: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1990: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsB cell development / Stromal cell / c-kit / SLF / IL-7 / immunoglobulin / μ鎖 / 血液幹細胞 / エレ-ヌ / cーkit / 免疫グロブリン / scidマウス / トランスジェニックマウス
Research Abstract

The major Purpose of this project is to understand cellular and molecular basis which regulates the early process of B cell differentiation in murine bone marrow. Before this project had started, we demonstrated that the entire process of B lineage differentiation from phuripotent hematopoietic stem cells to smu^+ mature B cells is supported by interleukin-7 (IL-7) and IL-7 negative stromal cell clone PA6. Using these two signals separately, intramarrow B lineage cells are divided into 4 distinct differentiation stages ; 1) B-pro-I which proliferates on the PA6-layer in the absence of IL-7, 2) B-pro II whose proliferation requires both PA6 and IL-7, 3) CFU-IL7 which proliferates in response to IL-7, and mature B cell which does not react to any of stromal cell-derived growth factors. On this basis, we next focused on following two subjects ; the role of c-kit and its ligand SLF in the stromal cell dependent B cell differentiation, and signals which triggers B cell differentiation. Foll … More owings are the summaries on the results obtained from this two year study.
1) There exists a distinct B lineage population which coexpresses c-kit and a B lineage marker, B220. From in vitro culture of FACS purified stem cell enriched population, B lineage differentiation proceeds from c-kit^+lin^- stem cell through c-kit^+B220^+ stage to c-kit^-B220^+ stage.
2) In vitro development of B lineage cells from c-kit^+lin^- stem cells is severely suppressed by addition of monoclonal antibody antagonistic to c-kit function. This suggests that c-kit on the early B cell surface in functional.
3) Most of B lineage cells in the bone marrow of scid mouse which is unable to express functional mu-chain express c-kit, while in the scid mouse carrying mu-chain transgene the most B cells do not express c-kit. This result suggests that c-kit expression is downregulated upon expression of mu-chain.
4) The frequency analysis of B-pro-II and CFU-IL7 in mu-transgenic mouse and k-transgenic mouse demonstrated that B-pro-II is selectively reduced in mu-transgenic mouse, while CFU-IL7 is selectively reduced in k-transgenic mouse. This result strongly suggests that the differentiation of B cells is directed by the expression of immunogrlobulin gene. Less

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Takahiro Kunisada: "IL-7 and B lymphopoiesis" Chemical Immunol. 51. 205-235 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Antonius Rolinks: "The C-kit-encoded tyrosine kinase regulates the proliferation of earley pre-B cells" Eur.J.mmunol.21. 2609-2612 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Makoto Naito: "Abnormal differentiation of tissue macrophage population in ostepretrosis (op)mice defective in the production of macrophage colony stimulating factor." Am.J.Immunol. 139. 657-667 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yasuhisa Matui: "Steel factor,the ligand for c-Kit,is necessary.but not sufficient for the proliferation of murine primordial germ cells." Nature. 353. 750-752 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yuji Gunji: "Support of early B-cell differentiation in mouse fetal liver by stromal cells and interleukin-7." Blood. 77. 2612-2617 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Akira Ohara: "Generation of B lymphocytes from a single hemopoietic progenitor cell in vitro." Int.Immunol.3. 703-709 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Seiji Okada: "Enrichment and characterization of murine hematopoietic stem cells that express c-kit molecule" Blood. 78. 1706-1712 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kazuya Yoshinaga: "Role of c-kit in a mouse spermatogenesis;Identification of spermatogonia as aspecific site for c-kit expression and function." Development. 113. 689-699 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Satomi Nishikawa: "In utero manipulation of coat color formation by a monoclonal anti-c-kit antibody;Two distinct waves of c-kit dependency during melanocyte development." The EMBO J.10. 2111-2119 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Minetaro Ogawa: "Exprassion and function of c-kit in hemopoietic progenitor cells." J.Exp.Med.174. 63-71 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shin-Ichi Hayashi: "Exon skipping by mutation of an authentic splice site of c-kit gene in w/w mouse." Nucleic Acid Res.19. 1267-1271 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takeshi Tubata: "Molecular and Cellular aspects of B-cell development." Current Opinion in Immunol.3. 186-192 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kunisada T., Nishikawa S, Ogawa M., Hayashi SI, Nishikawa SI: "IL-7 and B lymphopoiesis." Chemical Immunol. 51. 205-235 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Rolink A, Streb M, Nishikawa SI, Melchers F: "The c-kit encoded tyrosine kinase regulates the proliferation of early pre-B cells." Eur. J. Immunol.21. 2609-2612 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Naito M, Hayashi SI, Yoshida H, Nishikawa SI, Shultz LD, Takahashi K: "Abnormal differentiation of tissue macrophage population in osteopetrosis (op) mice defective in the production of macrophage colony stimulating factor." Am. J. Pathol.139.657-667 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Matsui Y, Toksoz D, Nishikawa S, Nishikawa SI, Williams D, Zsebo K, Hogan B: "Steel factor, the ligand for c-kit, is necessary, but not sufficient for the proliferation of murine primordial germ cells." Nature. 353. 750-752 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Gunji Y, Sudo T, Suda J, Yamaguchi Y, Nakauchi H, Nishikawa SI, Yanai N, Obinata M, Yanagisawa M, Miura Y, Suda T: "Support of early B-cell differentiation in mouse fetal liver by stromal cells and interleukin-7." Blood. 77. 2612-2617 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ohara A, Suda T, Tokuyama N, Suda J, Nakayama KI, Miura Y, Nishikawa SI, Nakauchi H: "Generation of B lymphocytes from a single hemopoietic progenitor cell in vitro." Int. Immunol.3. 703-709 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Okada S., Nakauchi H, Nagayoshi K, Nishikawa S, Nishikawa SI, Miura Y, Suda T: "Enrichment and characterization of murine hematopoietic stem cells that express c-kit molecule." Blood. 78. 1706-1712 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yoshinaga K., Nishikawa S, Ogawa M, Hayashi T, Kunisada T, Fujimoto T., Nishikawa SI.: "Pole of c-kit in mouse spermatogenesis : Identification of spermatogonia as a specific site for c-kit expression and function." Development. 113. 689 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Nishikawa S, Kusakabe M, Yoshinaga K, Ogawa M, Hayashi SI, Kunisada T, Era T, Sakakura T, Nishikawa SI: "In uteromanipulation of coat color formation by a monoclonal anti-c-kit antibody : Two distinct waves of c-kit dependency during melanocyte development." The EMBO J.10. 2111-2119 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ogawa M, Matsuzaki Y, Nishikawa S, Hayashi SI, Kunisada T, Sudo T, Kina T, Nakauchi H, Nishikawa SI: "Expression and function of c-kit in hemopoietic progenitor cells." J. Exp. Med.174. 63-71 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hayashi SI, Kunisada T, Ogawa M, Yamaguchi K, Nishikawa SI: "Exonskipping by mutation of an authentic splice site of c-kit gene in W/W mouse." Nucleic Acid Res.19. 1267-1271 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tsubata T, Nishikawa SI: "Molecular and Cellular aspects of early B-cell development." Current Opinion in Immunol.3. 186-192 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kodama H, Iizuka M, Tomiyama Y, Yoshida K, Seki M, Suda T, Nishikawa SI: "Response of newly established mouse myeloid leukemia cell lines in MC3T3-G2/PA6 preadipocytes and hemopoietic growth factors." Blood. 177. 49-54 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Era T., Ogawa M, Nishikawa SI, Okamoto M, Honjo T., Agagi K., Miyazaki JI., Yamamura K: "Differentiation of growth signal requirement of B lymphocyte precursor is directed by expression of immunoglobulin." The EMBO J.10. 337-342 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hayashi SI., Kunisada T., Ogawa M., Sudo T., Kodama H., Suda T., Nishikawa S., Nishikawa SI.: "Stepwise progression of B lineage differentiation supported by interleukin 7 and other stromal cell molecules." J. Exp. Med.171. 1863-1695 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yoshida H, Hayashi SI., Kunisada T., Ogawa M., Nishikawa S., Okamura H., Sudo T., Shultz LD., Nishikawa SI.: "The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene." Nature. 345. 441-442 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takahiro kunisada: "ILー7 and B lymphopoiesis" Chemical Immunol. 51. 205-235 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Antonius Rolinks: "The cーkitーencoded tyrosine Kinase regulates the proliferation of earley preーB Cells" Eur.J.Immunol.21. 2609-2612 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Makoto Naito: "Abnormal differentiation of tissue macrophage population in osteopetrosis(op)mice defective in the production of macrophage colony stimulating factor." Am.J.Immunol. 139. 657-667 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yasuhisa Matui: "Steel factor,the ligand for cーkit,is necessary,but not sufficient for the proliferation of murine primordial germ cells." Nature. 353. 750-752 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yuji Gunji: "Support of early BーCell differentiation in mouse fetal liver by stromal cells and interleukinー7." Blood. 77. 2612-2617 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Akira Ohara: "Generation of B lymphocytes from a single hemopoietic progenitor cell in vitro." Int.Immunol.3. 703-709 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Seiji Okada: "Enrichment and characterization of murine hematopoietic stem cells that express cーkit molecule" Blood. 78. 1706-1712 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] kazuya Yoshinaga: "Role of cーkit in mouse spermatogenesis;Identification of spermatogonia as aspecific site for cーkit expression and function." Development. 113. 689-699 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Satomi Nishikawa: "In utero manipulation of coat color formation by a monoclonal antiーcーkit antibody;Two distinct waves of cーkit dependency during melanocyte development." The EMBO J.10. 2111-2119 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Minetaro Ogawa: "Expression and function of cーkit in hemopoietic progenitor cells." J.Exp.Med.174. 63-71 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] ShinーIchi Hayashi: "Exon Skipping by mutation of an authentic splice site of cーkit gene in W/W_ー mouse." Nucleic Acid Res.19. 1267-1271 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takeshi Tubata: "Molecular and cellular aspects of Bーcell development." Current Opinion in Immunol.3. 186-192 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hiroaki Kodama: "Response of newly established mouse myeloid leukemia cell lines in MC3T3ーG2/PA6 preadipocytes and hematopoーietic growth factors." Blood. 177. 49-54 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takumi Era: "Differentiation of growth signal requirement of B lymphocyte precursor is directed by expression of immunoglobulin." The EMBO J.10. 337-342 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 江良 択実: "Differentiation of growth signal requirement of B cell precursor is directed by expression of immunoglobulin." The EMBO J.10. 337-342 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 山田 源: "Specific depletion of the B cell popuolation induced by aberrant expression of human IRFー1(interferon regulatory factorー1) gene in transgenic mice." Proc.Natl.Acad.Sci.USA.88. 532-536 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 鍔田 武志: "Molecular and cellular aspects of early Bーcell development." Current Opinion in Immunol.3/2. IN PRESS (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 国貞 隆弘: "ILー7 and B lymphopoiesis" Prog.Allergy. IN PRESS (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 林 眞一: "Stepwise progression of B lineage differentiation supported by interleukin 7 and other stromal cell molecules." J.Exp.Med.171. 1683-1695 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 吉田 尚弘: "The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene." Nature. 345. 441-442 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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