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Mechanism of B cell maturaion

Research Project

Project/Area Number 07457089
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionNational Institute of Health

Principal Investigator

TAKEMORI Toshitada  National Institute of Health, Department of Immunology, Director, 免疫部, 部長 (60114295)

Co-Investigator(Kenkyū-buntansha) ADACHI Yoshihiro  National Institute of Health, Department of Immunology, Investigator, 免疫部, 研究員 (20291122)
NAGAOKA Hitoshi  National Institute of Health, Department of Immunology, Investigator, 免疫部, 研究員 (20270647)
KASHIWADA Masaki  National Institute of Health, Department of Immunology, Investigator, 免疫部, 研究員 (20270639)
木元 博史  国立予防衛生研究所, 免疫部, 研究員 (20225080)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsprimary follicles / CD40 / MAP kinase / TRAF / germinal center / cell cycle / somatic hypermutation / antigen presentation / 細胞周期 / 一次免疫反応 / centroblast / 体細胞点変異 / Bリンパ球 / centrocyte / 記憶Bリンパ球 / 免疫グロブリン遺伝子
Research Abstract

A/WySnJ mouse. a subline of A/J,is known to be deficient in B cell maturation. We observed in the present study that formation of the primary follicle in the spleen is deficient in A/WySnJ mouse, as compared to A/J,which could be associated with deficiency in signal cascade including MAPK/ERK in the B cells, resulting in poor response to CD40 and IgM stimulation in vitro.
CD40 stimulation is essential for B cell activation and differentiation, such as class-switch, germinal center formation, and generation of memory. We observed in the present study that cd40 stimulation resulted in activation of MAPK/ERK via Ras-Raf-1-MEK signal pathway. The cytoplasmic tail of CD40 associates with TRAF2, TRAF3, TRAF5, and TRAF6. These TRAF proteins with exception for TRAF3 play a role in NF_KB activation in CD40 signaling. Our biochemical study showed that TRAF3 could inhibit MAPK/ERK activation in CD40 signaling. As overexpression of TRAF3 is known to suppress function of other TRAF proteins, the result is compatible with the idea that the TRAF protein as yet to be defined plays a role in MAPK/ERK activation in CD40 signaling.
After activation, B cells enter into the primary follicles and establish germinal center. We observed that, in contrast to well-developed germinal center, Ig+ germinal center B cells are mostly in cell cycling. There cells expand and occupy germinal center at high frequency on day 7-8 after immunization ; however, these cycling B cells rapidly reduced the number on day 8-10 postimmunization.
During that time these cells accumulate somatic hypermutation and could be selected by antigen. Rapidly cycling Ig+ germinal center B cells have potent antigen-presenting activity in vitro, suggesting that somatic hypermutation and antigen selection may operate simultaneously, probable via activation through T-cell interaction.

Report

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

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Kimoto,H.,Nagaoka,H.,Adachi,Y.,Yagi,T.,Azuma,T.,Sata,T.,Yonehara,S.,Tsunetsugu-Yokota,Y.,Taniguchi,M.and Takemori,T.: "Accumulation of somatic hypermutation and antigen-driven selection in rapidly cycling surface Ig+ germinal center (GC) B cells which occupy GC at a high frequency during the primary anti hapten response in mice." Eur.J.Immunol.27. 268-279 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kashiwada,M.,Kaneko,Y.,Yagita,H.,Okumura,K.and Takemori,T.: "Activation of mitogen-activated protein kinases via CD40 is distinct from that stimulated by surface IgM on B cells." Eur.J.Immunol.26. 1451-1458 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Misawa,Y.,Nagaoka,H.,Kimoto,H.,Kobayashi M.,Shibuya,M.,and Takemori,T.: "CD43 expression in a B cell lymphoma,WEHI 231,reduces susceptibility to G1 arrest and extends survival in culture upon serum depletion." Eur.J.Immunol.26. 2573-2581 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hagiwara,S.,Tsunetsugu-Yokota,Y.,Kimoto,H.and Takemori,T.: "Expression of VpreB3(8HS-20)molecules by alternative RNA processing." Int.Immunol.8. 1237-1244 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kimoto,H.,Nagaoka,H.,Adachi,Y.,Yagi,T.,Azuma,T.,Sata,T.,Yonehara,S.,Tsunetsugu-Yokota,Y.,Taniguchi,M.and Takemori,T.: "Accumulation of somatic hypermutation and antigen-driven selection in rapidly cycling surface Ig^+ germinal center (GC) B cells which occupy GC at a high frequency during the primary anti hapten response in mice." Eur.J.Immunol.27. 268-279 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kashiwada,M.,Kaneko,Y.,Yagita,H.,Okumura,K.and Takemori,T.: "Activation of mitogen-activated protein kinases via CD40 is distinct from that stimulated by surface IgM on B cells." Eur.J.Immunol.26. 1451-1458 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Misawa,Y.,Nagaoka,H.,Kimoto,H.,Kobayashi,M.,Shibuya,M.,and Takemori,T.: "CD43 expression in a B cell lymphoma,WEHI 231,reduces susceptibility to G1 arrest and extends survival in culture upon serum depletion." Eur.J.Immunol.26. 2573-2581 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hagiwara,S.,Tsunetsugu-Yokota,Y.,Kimoto,H.and Takemori,T.: "Expression of VpreB3 (8HS-20) molecules by alternative RNA processing." Int.Immunol.8. 1237-1244 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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