This finding highlights the potential for an autoantibody-independent effect of B cell depletion on MS disease activity. B cells are important antigen-presenting cells. Physical interaction of B cells and T cells [major histocompatibility complex (MHC)/antigen/T cell receptor] occurs in the presence of co-stimulatory molecules such as CD40/CD40ligand, B7/CD28, OX40 ligand/OX40 on the surface of B cells and T cells, respectively [55]. B cell depletion in mice was found to impact on

CD4+ T cell activation and expansion in vivo, which may explain its positive effect on multiple T cell-mediated autoimmune diseases, including MS [56] and type 1 diabetes [57]. It remains to be seen whether B cell-depleting strategies may alter the ratio of CTL : infected targets cells favourably, and thus enable better control of EBV infection. Furthermore, B cells have the ability to regulate T cell function and inflammation through cytokine production. A recent Y27632 study

found that B cells of MS patients had altered cytokine responses, e.g. increased ratio of lymphotoxin (LT) : IL-10 and increased secretion of tumour necrosis factor (TNF)-α and LT when exposed to the proinflammatory cytokine IFN-γ or bacterial cytosine–guanine dinucleotide (CpG)-DNA bound to Toll-like receptor 9 [58]. Interestingly, CD4 and CD8 T cells of MS patients produced significantly fewer proinflammatory Th1/Th17 cytokines after in vivo or ex vivo B cell depletion. B cell depletion may, therefore, be effective in reducing CNS inflammation. However, this website 4-Aminobutyrate aminotransferase B cells also play an important role in immunoregulation. Animal studies highlight the importance of the IL-10-producing B cell subset (B10) in the suppression of autoimmunity and inflammation [59], which may explain why B cell depletion led to the worsening of inflammatory disease in some EAE models, with delayed production of IL-10 and emergence of regulatory T cells [60]. B cell depletion also exacerbated disease in myelin–oligodendrocyte glycoprotein peptide (MOG p35–55)-induced EAE in mice [61]. Hence, the relative

contribution of B cells to EAE and MS may vary depending on the stage of disease progression, highlighting the existence of an intricate cross-talk between T and B cells. Exciting MS treatments are currently in the pipeline, which reflect important roles for B cells as drivers of MS pathogenesis, an area overshadowed by the emphasis on T cell research in the last decade. Furthermore, the eradication of EBV+ B cells by B cell-depleting strategies is another interesting line of investigation. B cell depletion may also impact on the propensity of latent infections to contribute to neuroinflammation in the CNS, and we may want to test anti-viral strategies in MS directly using drugs which can cross the blood–brain barrier; however, treatment success may also depend on the stage of disease progression.