Abstract
B Cell Maturation Antigen (BCMA) is a receptor expressed on plasma cells (PCs) and is important for the survival of long-lived PCs in the bone marrow. Our laboratory has shown that autoimmune-prone mice deficient in BCMA (lpr.BCMA-/-) develop an exacerbated autoimmune phenotype, including increased numbers of PCs, T cells, and serum autoantibody IgG titers. We recently determined that these mice also have increased total and auto-antigen specific serum IgA titers. Because IgA is normally produced in the mucosa-associated lymphoid tissue, this observation suggests a loss of tolerance in the intestinal mucosa. Based on these data, we hypothesized that BCMA signaling regulates homeostasis between commensal bacteria and the protective intestinal IgA response. We found that lpr.BCMA-/- mice have increased serum secretory IgA and commensal-specific IgA levels compared to controls. However, this was not due to increased intestinal permeability as assessed by a serum FITC dextran assay. To determine if commensal bacteria regulate peripheral IgA responses, lpr.BCMA-/- mice were placed on a one month antibiotic regimen. This regimen ameliorated autoimmune disease and reduced IgA-producing PCs, including both autoantibody and commensal-specific IgA. These results suggest that BCMA is important for the regulation of intestinal mucosal tolerance in our models, elucidating a previously unknown role for BCMA in maintaining the balance between commensals and the adaptive immune response.
