B cell function impacts the efficacy of IFN-β therapy in EAE

Agnieshka M Agasing,Saurabh Gawde,Gaurav Kumar,Emma Turner,Robert C Axtell

doi:10.1016/j.jneuroim.2019.577106

Abstract

Recent studies identified that interferon beta (IFN-β) treatment skews B-cells towards a regulatory phenotype in multiple sclerosis. To assess B cell involvement during IFN-β therapy, we compared IFN-β treatment in a B cell-independent model and a B cell-dependent model of experimental autoimmune encephalomyelitis (EAE). We show that in B cell-independent EAE, IFN-β ameliorates neuroinflammation. Conversely, in B cell-dependent EAE, IFN-β has no effect on disease. Effective IFN-β therapy in B cell-independent EAE was associated with reduced inflammatory T cells in the CNS and skewed splenic B cells towards an immature population and away from a germinal center population. These immune cell populations were unchanged in B cell-dependent EAE. Finally, we found that IFN-β increased marginal zone B cells in both EAE models. These findings indicate that B cell function impacts IFN-β efficacy during neuroinflammation.

Highlights

Multiple sclerosis (MS) is an autoimmune demyelinating disorder characterized by inflammation of the central nervous system (CNS) and neuronal demyelination
In rpMOG-EAE, we found that interferon beta (IFN-β) significantly increased the immature/transitional (IgM+IgDlo) and marginal zone (MZ) B cell populations and decreased germinal center (GC) B cells (Fig. 4a)
We show for the first time that IFN-β has no effect on human MOG1–125 protein (hMOG)-induced EAE, where B cells play an inflammatory role

Summary

Introduction

Multiple sclerosis (MS) is an autoimmune demyelinating disorder characterized by inflammation of the central nervous system (CNS) and neuronal demyelination. Relapsing-remitting MS (RRMS) is the most common form of MS and is characterized by alternating episodes of relapses and recovery. Interferon beta (IFN-β) was the first disease-modifying drug developed for RRMS. IFN-β has a strong safety profile and significantly reduces disease activity in the general MS population (Group, T.I.M.S.S, 1993). Approximately 30% of RRMS patients respond poorly to IFN-β. The therapeutic mechanism of IFN-β in MS remains unclear. Studies from our lab and others indicate that IFN-β has either pro-inflammatory or anti-inflammatory effects, depending on disease context (Axtell et al, 2010; Hegen et al, 2016; Palace et al, 2010; Paty and Li, 1993)

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Conclusion