B cells from relapsing remitting multiple sclerosis patients modulate T cell behaviorin a neuroantigen-specific manner

The role of B cells in the pathoetiology of relapsing remitting multiple sclerosis is not well understood. B cells may contribute to MS by antibody secretion, cytokine production and antigen presentation. Antigen-specific B cells are highly efficient antigen presenting cells in the context of their cognate antigens. Since antibodies from multiple sclerosis patients bind to neuroantigens we hypothesized that neuroantigen specific memory B cells promote disease in multiple sclerosis patients by serving as antigen presenting cells for auto-reactive T cells. We observed that B cells from a subset of multiple sclerosis patients induce naive and memory T cell proliferation in the presence of recombinant neuroantigens, myelin oligodendrocyte glycoprotein and myelin basic protein, but not MOG 35-55 peptide, in B-T cell co-cultures. Similarly, in the presence of neuroantigen proteins cells from multiple sclerosis patients secreted greater levels of IFN-γ, IL-6, -17A, -17F, -21, -22, -31, -33, TNF-α and soluble CD40L than healthy donors, while levels of IL-4 and IL-25 were similar. These data support a role for human B cells as antigen presenting cells in multiple sclerosis and highlight the role of B cells in the context of autoimmune disease beyond antibody production.