BAFF and APRIL signaling through BCMA regulates microglial cells in the central nervous system.

Abstract

Abstract B cell Maturation Antigen (BCMA) is a receptor that engages the cytokines BAFF and APRIL. BCMA is known to play a critical role in regulating B cell proliferation, survival, and differentiation into plasma cells. However, the effect of BCMA on non-B cells has been understudied. We have previously shown that BCMA regulates EAE, where BCMA −/−mice have exacerbated disease compared to BCMA +/+mice. The increased disease in the BCMA −/−mice was associated with increased infiltration of B cells, T cells and inflammatory macrophages in the central nervous system (CNS). In this study, we assessed the expression patterns of BCMA on different immune cell types infiltrating the CNS of mice with EAE by flow cytometry. We found BCMA is expressed on plasma cells, microglia and inflammatory macrophages that are in the CNS, but not T cells or neutrophils. Next, we compared the numbers and phenotype of different myeloid cells in the CNS and lymph nodes in healthy BCMA −/−and BCMA +/+mice. We found that BCMA −/−mice have an increased number of resident microglial cells with low CD86 expression in the brain compared to BCMA +/+mice. Also, we found elevated numbers of macrophages with M1 (measured by the expression of iNOS) phenotype in the brain of BCMA −/−mice compared to BCMA +/+mice. In lymph nodes, we found an increased number of M1 type macrophages in the BCMA −/−in comparison to BCMA +/+mice with low CD86 expression. These data suggest a novel role for BCMA in regulating the phenotype and function of microglial and macrophages in CNS and in the peripheral immune tissues. Our data points towards a new pathway regulated by BAFF and APRIL signaling through BCMA and provides clues behind the immunopathogenesis of neuroautoimmune diseases. This study was supported by grants from the NMSS (RG-1602-07722), the NIH (R01AI137047 and R01EY027346) awarded to R.C. Axtell.