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生发中心细胞上抑制性IgG Fc受体FcγRIIB的差异表达:对高亲和力B细胞选择的影响

Differential expression of the inhibitory IgG Fc receptor FcgammaRIIB on germinal center cells: implications for selection of high-affinity B cells.

作者信息

Rao Sambasiva P, Vora Kalpit A, Manser Tim

机构信息

Kimmel Cancer Center and Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.

出版信息

J Immunol. 2002 Aug 15;169(4):1859-68. doi: 10.4049/jimmunol.169.4.1859.

Abstract

The murine low-affinity receptor for IgG, FcgammaRIIB, mediates inhibition of B cell receptor-triggered events in primary B cells. We investigated the expression of FcgammaRIIB on germinal center (GC) cells to better understand its role in memory B cell development. Immunohistological analyses demonstrated differential regulation of FcgammaRIIB on GC cells. Its levels are markedly down-regulated on GC B cells and up-regulated on follicular dendritic cells (FDC) at all times during the GC response. Analyses of surface expression of FcgammaRIIB by flow cytometry and FcgammaRIIB mRNA levels by RT-PCR analysis confirmed that this FcR is down-regulated in GC B cells. In mice lacking FcgammaRIIB, the development of the secondary FDC reticulum in GCs is substantially delayed, although the overall kinetics of the GC response are unaltered. These findings have direct implications for models proposed to account for the selection of high-affinity B cells in the GC and suggest a role for FcgammaRIIB in promoting the maturation of the FDC reticulum.

摘要

小鼠IgG低亲和力受体FcγRIIB介导对原代B细胞中B细胞受体触发事件的抑制。我们研究了FcγRIIB在生发中心(GC)细胞上的表达,以更好地了解其在记忆B细胞发育中的作用。免疫组织学分析表明,GC细胞上FcγRIIB的调节存在差异。在GC反应的所有阶段,其水平在GC B细胞上显著下调,而在滤泡树突状细胞(FDC)上上调。通过流式细胞术分析FcγRIIB的表面表达以及通过RT-PCR分析FcγRIIB mRNA水平,证实该FcR在GC B细胞中下调。在缺乏FcγRIIB的小鼠中,GC中次级FDC网状结构的发育显著延迟,尽管GC反应的总体动力学未改变。这些发现对解释GC中高亲和力B细胞选择的模型有直接影响,并提示FcγRIIB在促进FDC网状结构成熟中发挥作用。

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