B cell intrinsic effects of the vitamin D receptor on IgE responses. (IRC10P.417)

Abstract

Abstract B cells express the vitamin D receptor (VDR). VDR KO mice had higher levels of circulating total IgE than WT mice by 12 wks of age. Mice were sensitized using two OVA/alum injections. VDR KO mice mounted a significantly higher OVA-specific IgE response compared to WT mice. The data also showed that vitamin D deficient mice had higher OVA-specific IgE responses than vitamin D sufficient mice. IL-4, IL-5, IL-2, IFN-γ and IL-17 were not different in OVA re-stimulated spleen and mesenteric lymph nodes (MLN) in WT and VDR KO mice. However, VDR KO spleen and MLN produced significantly less IL-10 than WT. Furthermore B cells and not T cells were the major source of IL-10 in both the WT and VDR KO cultures. Experiments were done using T cell specific-VDR deletion (T-VDR KO), or B cell specific-VDR deletion (B-VDR KO). The serum IgE levels in T-VDR KO mice were comparable to that of WT mice. Conversely, B-VDR KO mice had higher total serum IgE levels than WT mice and, when immunized, produced significantly more OVA-IgE. In our current model, we propose that B cell-derived IL-10 is regulated by the VDR and that autocrine IL-10 is higher in WT mice, therefore inhibiting IgE production to a greater extent in WT than in VDR KO mice. The major finding of this work is that vitamin D receptor expression selectively regulates IgE levels in the serum via a direct effect of the VDR in B cells.