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

Abstract

FcgammaRIIB, a low-affinity FcR for IgG, inhibits BCR-mediated activation when these two receptors are co-cross-linked by Ags and IgG-containing immune complexes. Although a role for FcgammaRIIB in the germinal center (GC) reaction has been proposed, conflicting results have been published regarding the levels of FcgammaRIIB 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 FcgammaRIIB from follicular dendritic cells. Our results are in concordance with previous data indicating that FcgammaRIIB expression is up-regulated on GC B cells in normal mice. In contrast, we observe comparable levels of FcgammaRIIB 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 FcgammaRIIB 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 FcgammaRIIB gene but does appear to be independent of genetic background. Finally, we present evidence indicating that FcgammaRIII, a low-affinity activating IgG FcR, is expressed on the GC B cells of normal but not autoimmune-prone mice.