B Cells Promote Induction of Experimental Autoimmune Encephalomyelitis by Facilitating Reactivation of T Cells in the Central Nervous System

The efficacy of rituximab treatment in multiple sclerosis has renewed interest in the role of B cells in CNS autoimmunity. In this study, we show that B cells are the predominant MHC class II+ subset in the naive CNS in mice, and they constitutively express proinflammatory cytokines. Incidence of experimental autoimmune encephalomyelitis induced by adoptive transfer was significantly reduced in C3HeB/Fej mu MT (B cell-deficient) mice, suggesting an important role for CNS B cells in initiating inflammatory responses. Initial T cell infiltration of the CNS occurred normally in mu MT mice; however, lack of production of T cell cytokines and other immune mediators indicated impaired T cell reactivation. Subsequent recruitment of immune cells from the periphery driven by this initial T cell reactivation did not occur in mu MT mice. B cells required exogenous IL-1 beta to reactivate Th17 but not Th1 cells in vitro. Similarly, reactivation of Th1 cells infiltrating the CNS was selectively impaired compared with Th17 cells in mu MT mice, causing an increased Th17/Th1 ratio in the CNS at experimental autoimmune encephalomyelitis onset and enhanced brain inflammation. These studies reveal an important role for B cells within the CNS in reactivating T cells and influencing the clinical manifestation of disease.