Autoimmune neurologic diseases
B-cell depletion therapy (BCDT) substantially reduces new disease activity in multiple sclerosis (MS), without impacting the abnormal cerebrospinal fluid immunoglobulin levels. Recent work has demonstrated that B cells engage in bi-directional interactions with CD4+ T cells, and contribute to their abnormal immune responses in MS as substantiated by findings that T-cell effector functions are attenuated in individuals receiving BCDT. Curiously, BCDT is also found to decrease CD8+ T cell responses, and B cells and CD8+ T cells (including mucosal associated invariant T (MAIT) cells), are found together within the MS central nervous system (CNS). Little is known about interactions between B cells and CD8+ T cells, including MAIT cells. To this end, we generated an in vitro cell culture system, in which human polyclonally activated CD8+ T cells are co-cultured with autologous B cells. We found that while primed B cells suppressed the proliferation of naïve CD8+ T cells, they enhanced the proliferation of CD8+ MAIT cells. Primed B cells also selectively boosted MAIT-cell degranulation and cytotoxicity. These effects were not contact-dependent and involved B-cell derived soluble factors. In turn, activated CD8+ T cells enhanced B-cell cytokine production. Together this data indicates cross-talk may exist between B cells and CD8+ T cells, including the capacity of B cells to reciprocally impact distinct CD8+ T cell subsets. The particular capacity of B cells to induce activation and effector responses of MAIT cells may be relevant to MS pathophysiology and to the therapeutic mode of action of BCDT in MS.