Contribution of memory and naive B cells to myelin specific T cell function in relapsing remitting multiple sclerosis

Abstract B cell depletion therapy reduces numbers of B and T cells within the cerebrospinal fluid (CSF) of relapsing remitting multiple sclerosis (RRMS) patients, suggesting that reduction of CSF B cells modulates the T cell pool in RRMS. We hypothesized that T-B cell interactions are required in order for myelin reactive T cells to proliferate and secrete cytokines optimally, and that memory B cells would be more effective APCs than naïve B cells, because of their higher expression of co-stimulatory molecules and high affinity B cell receptors. To test this hypothesis, we sorted naïve (CD19+CD27-) and memory (CD19+CD27+) B cells from the peripheral blood of 12 treatment naïve RRMS patients, incubated them with autologous purified T cells in the presence of myelin-derived proteins or control recall antigens, and measured T cell proliferation and cytokine production. Both naïve and memory B cells elicited CD4+ and CD8+ T cell proliferation and IFN-gamma secretion to recall antigens, although memory B cells from these patients elicited greater myelin specific CD4+ T cell proliferation than naïve B cells. These data suggest that in a subset of RRMS patients, the memory B cell pool has an enhanced ability to induce activation of myelin specific T cells, most likely because the memory B cell pool is enriched for B cells that have undergone myelin specific affinity driven maturation. This work was supported by Teva Neuroscience.