IFNbeta-1b Treatment Alters the Composition of Circulating B Cell Subsets and Leads to Changes in the B Cell Cytokine Secretion Profile in an Ex-vivo Stimulation Assay for Patients with Relapsing-Remitting Multiple Sclerosis

Recent studies provide strong evidence for a role for B cells in the pathology of relapsing-remitting multiple sclerosis (RRMS). To explore the effect of IFNbeta-1b treatment on B cell phenotype and function in these patients, blood was drawn from 10 RRMS patients before treatment and again 2 and 6 months after daily injections of IFNbeta-1b. Cryopreserved PBMCs were thawed and stained with panels of antibodies against B cell surface antigens. PBMCs were also stimulated with CpG-B. Stimulated cell surface phenotype as well as intracellular IL10 and IL6 were determined by 10-parameter flow cytometry. PBMCs from age and gender matched normal healthy donors were examined in parallel. At baseline, RRMS patients have significantly increased frequencies of naiive B cells and decreased frequencies of memory B cells when compared with healthy controls. CpG-B-stimulated PBMCs from patients treated with IFNbeta-1b show an increase in IL-10 production and a decrease in IL-6 production by naiive, memory and B1 cells (a recently-described subset of autoantibody producing cells that are CD20+CD27+CD43+). These changes in cytokine production are indicative of a change from a pro- to an anti-inflammatory phenotype. In addition, this treatment alters the composition of circulating B cell subsets, leading to an increase after six months in circulating naiive B cells and a decrease in both memory and B1 cells, both cell types of which are potentially pathogenic in RRMS. Although the number of subjects in this study was limited, these findings suggest that alterations in B cell phenotype and function may be a mechanism by which IFNbeta-1b reduces disease activity. Study Supported by: Bayer HealthCare Pharmaceuticals Inc.