IFNβ-1b treatment leads to changes in the B cell subset and cytokine secretion profile in patients with relapsing-remitting multiple sclerosis
Mielcarz, D. W.; Bergeron, A. J.; DeLong, J. K.; Dias, A.; Smith, K. M.; Mack, K. L.; Kasper, L. H.; Channon, J. Y.
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In order to explore the effect of IFN{beta}-1b treatment on B cell phenotype and function in RRMS patients, blood was drawn from RRMS patients before treatment and again 2 and 6 months after every other day injections of IFN{beta}-1b. Cryopreserved peripheral blood mononuclear cells (PBMCs) were thawed and stained with panels of antibodies against B cell surface antigens and the intracellular cytokines, IL-10 and IL-6. At baseline, PBMCs from RRMS patients have increased frequencies of B1 cells and a decreased frequencies of memory B cells when compared with PBMCs from age- and gender-matched healthy controls. CpG-stimulated PBMCs from patients treated with IFN{beta}-1b show an increase in IL-10 production and a decrease in IL-6 production by naive, memory and B1 cells compared with healthy controls. In addition, this treatment alters the composition of circulating B cell subsets, leading to an increase after six months in circulating naive B cells and a decrease in both memory and B1 cells, both cell types of which are potentially pathogenic in RRMS. Patients were divided into two groups based on disease activity, no/low or moderate/high. A significantly higher frequency of B1 cells and higher expression of CD27 on these cells was seen at baseline in the moderate/high disease activity group to IFN{beta}-1b compared with patients in the no/low disease activity group. Although the number of subjects in this study was limited, these findings suggest that alterations in the B cell compartment may be a mechanism by which IFN{beta}-1b reduces disease activity.
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