Circulating B Cells in Relapsing-Remitting Multiple Sclerosis Show Markedly Different Patterns of Regulatory Marker Expression Compared with Healthy Controls

Recent evidence has shown that B cells may play a key role in the pathogenesis of relapsing-remitting multiple sclerosis. Studies in our laboratory have shown a difference in the production of IL-6 and IL-10 by B cells isolated from RRMS patients compared with healthy controls. In order to further characterize the nature of the B cells in RRMS patients, we analyzed samples from patients on no disease modifying treatment for B cell expression of multiple phenotypic and regulatory markers. We observed an increased frequency in the number of circulating B cells, an increase in B1 B cells and a decrease in memory B cells in RRMS patients. These B1 cells showed a significantly higher frequency of CD5 expression and the memory B cells a significant increase in the class-switched IgD-phenotype. We also examined death receptors involved in apoptotic pathways. CD95 frequency was significantly lower in RRMS patients tan healthy controls in all B cell subsets. Conversely, frequency of PD-1 was elevated in both the naive and memory B cell subsets, and PD-L1 was elevated in B1 cells from RRMS patients. Finally, we examined a series of immunoreceptor tyrosine-based inhibition motif (ITIM)-containing inhibitory receptors, including members of the SIGLEC family. Significantly higher levels of CD22, CD305 and CD307d were seen in RRMS patients, while significantly lower levels of SIGLEC-10 were observed. Taken together, these results indicate a potential for differential regulation of B cells in RRMS patients that may provide an avenue for B cell directed therapies for the disease.