B cell antigen presentation is sufficient to drive neuro-inflammation in an animal model of multiple sclerosis (BA3P.120)

Abstract

Abstract B cells are increasingly regarded as integral to the pathogenesis of multiple sclerosis (MS). Several B cell-dependent mechanisms contributing to inflammatory demyelination of the central nervous system (CNS) have been explored using the CD4 T cell-dependent animal model for MS, experimental autoimmune encephalomyelitis (EAE). While B cell antigen presentation has been suggested to regulate CNS inflammation during EAE, no direct evidence that B cells independently support antigen-specific autoimmune responses by CD4 T cells in EAE exists. Using a newly generated murine model of in vivo conditional MHCII expression, we previously reported that encephalitogenic CD4 T cells are incapable of inducing EAE when B cells are the only antigen presenting cell expressing MHCII. Using this system we now find that B cells cooperate with dendritic cells to enhance active EAE severity resulting from myelin oligodendrocyte glycoprotein (MOG) immunization. Further, increasing the frequency of MOG-specific B cells, but not supplementation with soluble MOG-specific antibody, is sufficient to drive EAE in mice expressing MHCII solely by B cells. By temporally regulating MHCII expression in MOG-specific B cells, we find induction of EAE reliably occurs upon expression of MHCII. These data support a model in which the expansion of antigen-specific B cells during CNS autoimmunity amplifies cognate interactions between B and CD4 T cells and drives neuro-inflammation at later stages of disease.