Our understanding of the basic pathogenic mechanisms of MS has been radically changed by the emergence of novel immune-based treatments that have specifically targeted B cells. Because there is strong clinical and experimental evidence that B cells contribute to MS via their role as antigen presenting cells, we have used our conditional mouse system to explore the extent to which B cells alone can drive CD4 T cell auto-reactivity in vivo. In our preliminary studies, we have found that antigen presentation by B cells alone is not sufficient to support passive EAE resulting from transfer of encephalitogenic CD4 T cells, unless B cells also express antigen receptor specific for cognate antigen. Currently, we are exploring the mechanisms by which B cells drive CD4 T cell auto-reactivity during EAE and the role of B cell antigen presentation in meningeal ectopic lymphoid tissue development.