B cells are increasingly regarded as integral to the pathogenesis of multiple 
sclerosis, in part as a result of the success of B cell-depletion therapy. 
Multiple B cell-dependent mechanisms contributing to inflammatory demyelination 
of the CNS have been explored using experimental autoimmune encephalomyelitis 
(EAE), a CD4 T cell-dependent animal model for multiple sclerosis. Although B 
cell Ag presentation was suggested to regulate CNS inflammation during EAE, 
direct evidence that B cells can independently support Ag-specific autoimmune 
responses by CD4 T cells in EAE is lacking. Using a newly developed murine model 
of in vivo conditional expression of MHC class II, we reported previously that 
encephalitogenic CD4 T cells are incapable of inducing EAE when B cells are the 
sole APC. In this study, we find that B cells cooperate with dendritic cells to 
enhance EAE severity resulting from myelin oligodendrocyte glycoprotein (MOG) 
immunization. Further, increasing the precursor frequency of MOG-specific B 
cells, but not the addition of soluble MOG-specific Ab, is sufficient to drive 
EAE in mice expressing MHCII by B cells alone. These data support a model in 
which expansion of Ag-specific B cells during CNS autoimmunity amplifies cognate 
interactions between B and CD4 T cells and have the capacity to independently 
drive neuroinflammation at later stages of disease.