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B cell function impacts the efficacy of IFN- therapy in EAE

Agasing, AM;Gawde, S;Kumar, G;Turner, E;Axtell, RC;

Recent studies identified that interferon beta (IFN-) treatment skews B-cells towards a regulatory phenotype in multiple sclerosis. To assess B cell involvement during IFN- therapy, we compared IFN- treatment in a B cell-independent model and a B cell-dependent model of experimental autoimmune encephalomyelitis (EAE). We show that in B cell-independent EAE, IFN- ameliorates neuroinflammation. Conversely, in B cell-dependent EAE, IFN- has no effect on disease. Effective IFN- therapy in B cell-independent EAE was associated with reduced inflammatory T cells in the CNS and skewed splenic B cells towards an immature population and away from a germinal center population. These immune cell populations were unchanged in B cell-dependent EAE. Finally, we found that IFN- increased marginal zone B cells in both EAE models. These findings indicate that B cell function impacts IFN- efficacy during neuroinflammation.