B Cells Are Multifunctional Players in Multiple Sclerosis Pathogenesis: Insights from Therapeutic Interventions.

Nele Claes,Piet Stinissen,Raymond Hupperts,Raymond Hupperts,Veerle Somers,Judith Fraussen

doi:10.3389/fimmu.2015.00642

Nele Claes, Piet Stinissen + Show 4 more

Open Access

https://doi.org/10.3389/fimmu.2015.00642

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Abstract

Multiple sclerosis (MS) is a severe disease of the central nervous system (CNS) characterized by autoimmune inflammation and neurodegeneration. Historically, damage to the CNS was thought to be mediated predominantly by activated pro-inflammatory T cells. B cell involvement in the pathogenesis of MS was solely attributed to autoantibody production. The first clues for the involvement of antibody-independent B cell functions in MS pathology came from positive results in clinical trials of the B cell-depleting treatment rituximab in patients with relapsing-remitting (RR) MS. The survival of antibody-secreting plasma cells and decrease in T cell numbers indicated the importance of other B cell functions in MS such as antigen presentation, costimulation, and cytokine production. Rituximab provided us with an example of how clinical trials can lead to new research opportunities concerning B cell biology. Moreover, analysis of the antibody-independent B cell functions in MS has gained interest since these trials. Limited information is present on the effects of current immunomodulatory therapies on B cell functions, although effects of both first-line (interferon, glatiramer acetate, dimethyl fumarate, and teriflunomide), second-line (fingolimod, natalizumab), and even third-line (monoclonal antibody therapies) treatments on B cell subtype distribution, expression of functional surface markers, and secretion of different cytokines by B cells have been studied to some extent. In this review, we summarize the effects of different MS-related treatments on B cell functions that have been described up to now in order to find new research opportunities and contribute to the understanding of the pathogenesis of MS.

Highlights

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by demyelination in white and gray matter regions, axonal degeneration, and gliosis [1]
B cells are essential for antigen presentation and costimulation of T cells, for the production of cytokines and to produce antibodies that will target components of the CNS
Research on effects of therapy on B cell phenotype and function has demonstrated a shift from pro-inflammatory B cell functions toward more anti-inflammatory and regulatory functions

Summary

INTRODUCTION

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by demyelination in white and gray matter regions, axonal degeneration, and gliosis [1]. Autoreactive T cells are activated in the periphery most likely via molecular mimicry or bystander activation and home through a disrupted blood–brain barrier (BBB) to the CNS, where they are reactivated by antigen-presenting cells This triggers the production of different mediators, such as chemokines and cytokines, by T cells, microglia, and other cells of the CNS. Proof of B cell involvement in MS is described thoroughly further on in the review Both B cell subtype distribution and B cell effector functions are important contributors to the disease. These processes are first described in more detail in order to fully understand how these processes are affected in MS patients and modulated by different MS treatments

B Cell Subtype Distribution in MS

B Cell Effector Functions

Findings

CONCLUSION