I22 Regulatory B cells in healthy and in patients with sle

Abstract

Recent advances have demonstrated the existence of an IL-10-producing B cell subset with regulatory capacity named (Bregs). In mice, Bregs have been shown to restrain the severity of autoimmune disorders and contribute to the development of infection and cancer. In humans, CD19 + CD24 hi CD38 hi C D1d hi B cells have been ascribed with regulatory function. We have shown that this B cell subset inhibits the activation of T helper (Th)1 and Th17 responses whilst supporting the differentiation of FoxP3 + Tregs. We have shown that, in addition to regulating the differentiation of CD4 + T cells, Bregs are essential for the maintenance of CD1d-restricted invariant natural killer T ( i NKT) cells in healthy individuals but fail to exert the same effect in SLE patients. i NKT cells play a potent immune-regulatory role functioning in both innate and adaptive immunity. Defective B cell-mediated stimulation of i NKT cells in SLE was associated with rapid CD1d recycling leading to reduced CD1d surface expression on B cells from SLE patients, a defect that could be recapitulated in B cells from healthy individuals after simultaneous stimulation with interferon-a (IFN-a) and anti-immunoglobulin (Ig). i NKT cell homeostasis was restored in SLE patients responding to B cell depletion therapy, upon normalization of CD1d levels in repopulated CD19 + CD24 hi CD38 hi C D1d hi Bregs.