| Project/Area Number |
07457089
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | National Institute of Health |
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Principal Investigator |
TAKEMORI Toshitada National Institute of Health, Department of Immunology, Director, 免疫部, 部長 (60114295)
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| 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)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | primary 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 |
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| 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.
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