B cell maturation antigen impacts microglia and macrophage phenotypes in neuro-autoimmune disease 3920

Abstract Description BAFF and APRIL, crucial to B cell function, play a role in multiple sclerosis (MS), with therapeutic blockade linked to worsened disease. These cytokines signal through the receptors: BAFFR, TACI, and BCMA. BCMA stands out in MS due to elevated soluble levels in the cerebrospinal fluid. Our prior study using EAE revealed increased disease severity in BCMA knockout mice. Additionally, BCMA showed divergent roles in response to anti-CD20 and TACI-Fc treatments in EAE, enhancing anti-CD20 therapy responsiveness but diminishing TACI-Fc efficacy. The contrasting effects of BCMA on these treatments led us to explore its function in cell types beyond B cells. Here, we report that BCMA is highly expressed on microglial cells, and infiltrating Ly6C+ myeloid cells in the CNS of wildtype mice with EAE. Additionally, we found that BCMA-/- mice exhibited altered CD86 expression on microglial cells and elevated iNOS on infiltrating macrophages, suggesting a role in skewing towards an M1 phenotype in the CNS during EAE. In the lymph nodes, we also observed a similar effect on the M1-type macrophages in BCMA-/- mice compared to BCMA+/+ mice. These findings offer evidence of a novel role for BCMA in modulating microglia and macrophage function, providing additional insights into the intricate role that BAFF and APRIL play in neuroautoimmune diseases. Funding Sources NIH 1R01EY027346 National Multiple Sclerosis Society (RG-1602-07722) Center for Advancement of Science & Technology (OCAST) health research grant HR23-144 Topic Categories Therapeutic Approaches to Autoimmunity (THER)