Myelin-specific B cell receptor transgenic mice reveal critical role for B cell accessory function independent of antibodies in pathogenesis of CNS autoimmune disease (148.2)

Abstract

Abstract Human myelin oligodendrocyte glycoprotein (MOG) induces experimental autoimmune encephalomyelitis (EAE) in a B cell-dependent manner, and is associated with MOG-specific antibodies (Abs). Whether B cells serve as antigen presenting cells (APC) for activation of encephalitogenic MOG-specific T cells in EAE induced by MOG is unknown. To distinguish the role of APC function by MOG-specific B cells from MOG-specific Abs, we created MOG-specific B cell receptor (BCR) transgenic (Tg) mice containing B cells that express membrane MOG-specific Ig only (MOGmIg), but cannot secrete Abs. EAE was compared in MOGmIg mice, MOG-specific BCR knock-in (Th) mice that can secrete all isotypes, in B cell-deficient and wild-type (WT) mice. B cell-deficient mice were resistant, confirming the requirement for B cells in human MOG-induced EAE. MOG induced EAE in MOG BCR knock-in mice, WT mice and MOGmIg Tg mice, indicating that B cells provide an accessory (i.e. APC) function, independent of Ab secretion in MOG-induced EAE. To further evaluate B cell function, mixed bone marrow (bm) chimera mice were created that contained B cells that were selectively MHC II-deficient. Mixed bm chimera mice that contained MHC II+ B cells were susceptible to MOG-induced EAE, whereas mice containing MHC II- B cells were resistant, despite MHC II expression on other APC. Our results conclusively demonstrate that independent of their humoral role, B cells provide a critical cellular function in EAE pathogenesis.