Failed up-regulation of the inhibitory IgG Fc receptor FcγRIIB on germinal center B cells in autoimmune-prone mice is not associated with deletion polymorphisms in the promoter region of the FcγRIIB gene

被引:28
作者
Rahman, ZSM
Manser, T
机构
[1] Thomas Jefferson Univ, Jefferson Med Coll, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA
[2] Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Ctr, Philadelphia, PA 19107 USA
关键词
D O I
10.4049/jimmunol.175.3.1440
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Fc gamma RIIB, a low-affinity FcR for IgG, inhibits BCR-mediated activation when these two receptors are cocross-linked by Ags and IgG-containing immune complexes. Although a role for Fc gamma RIIB in the germinal center (GC) reaction has been proposed, conflicting results have been published regarding the levels of Fc gamma RIIB expressed on GC B cells in normal and autoimmune-prone mice and humans. In the present study, we investigate this issue in detail in mice by using multiple GC B cell markers, two different antigenic systems, primary and secondary GC responses, and by excluding the influence of splenic influx of immature B cells and passive acquisition of FcyRIIB from follicular dendritic cells. Our results are in concordance with previous data indicating that Fc gamma RIIB expression is up-regulated on GC B cells in normal mice. In contrast, we observe comparable levels of Fc gamma RIIB on GC and non-GC B cells in New Zealand White, New Zealand Black, and B6.Sle1 autoimmune-prone strains. Therefore, we suggest that these strains exhibit failed up-regulation of FcyRIIB on GC B cells, rather than down-regulation, as previously suggested. Also, in contrast to previous indications, this perturbed regulation is not uniquely associated with deletion polymorphisms in the promoter region of the Fc gamma RIIB gene but does appear to be independent of genetic background. Finally, we present evidence indicating that Fc gamma RII, a low-affinity activating IgG FcR, is expressed on the GC B cells of normal but not autoimmune-prone mice.
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页码:1440 / 1449
页数:10
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