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 naïve 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by funding from Bayer Healthcare Pharmeceuticals. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Geisel School of Medicine Institutional Review Board. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.