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Seminars in Immunopathology

, Volume 36, Issue 3, pp 339–350 | Cite as

B cells in MS and NMO: pathogenesis and therapy

  • Markus Krumbholz
  • Edgar Meinl
Review

Abstract

B linage cells are versatile players in multiple sclerosis (MS) and neuromyelitis optica/neuromyelitis optica spectrum disorder (NMO). New potential targets of autoantibodies have been described recently. Pathogenic mechanisms extend further to antigen presentation and cytokine production, which are increasingly recognized as therapeutic targets. In addition to pro-inflammatory effects of B cells, they may act also as anti-inflammatory via production of interleukin (IL)-10, IL-35, and other mechanisms. Definition of regulatory B cell subsets is an ongoing issue. Recent studies have provided evidence for a loss of B cell self-tolerance in MS. An immunogenetic approach demonstrated exchange of B cell clones between CSF and blood. The central nervous system (CNS) of MS patients fosters B cell survival, at least partly via BAFF and APRIL. The unexpected increase of relapses in a trial with a soluble BAFF/APRIL receptor (atacicept) suggests that this system is involved in MS, but with features that are not yet understood. In this review, we further discuss evidence for B cell and Ig contribution to human MS and NMO pathogenesis, pro-inflammatory and regulatory B cell effector functions, impaired B cell immune tolerance, the B cell-fostering microenvironment in the CNS, and B cell-targeted therapeutic interventions for MS and NMO, including CD20 depletion (rituximab, ocrelizumab, and ofatumumab), anti-IL6-R (tocilizumab), complement-blocking (eculizumab), inhibitors of AQP4-Ig binding (aquaporumab, small molecular compounds), and BAFF/BAFF-R-targeting agents.

Keywords

Multiple sclerosis Neuromyelitis optica B cells Antibodies Pathogenesis Therapy 

Abbreviations

MS

Multiple sclerosis

PP-MS

Primary progressive MS

RR-MS

Relapsing-remitting MS

SP-MS

Secondary progressive MS

NMO

Neuromyelitis optica/neuromyelitis optica spectrum disorder

RA

Rheumatoid arthritis

CNS

Central nervous system

IL

Interleukin

TNF

Tumor necrosis factor

TGF-β

Transforming growth factor β

LTα

Lymphotoxin α

EAE

Experimental autoimmune encephalomyelitis

AQP4

Aquaporin 4

MOG

Myelin oligodendrocyte glycoprotein

mAb

Monoclonal antibody

Notes

Acknowledgments

The work of the authors is supported by the Deutsche Forschungsgemeinschaft (SFB TR128), the Verein zur Therapieforschung für Multiple-Sklerose-Kranke, the Bundesministerium für Bildung und Forschung (“Krankheitsbezogenes Kompetenznetz Multiple Sklerose”), and the Gemeinnützige Hertie Stiftung.

Conflict of interest

E. Meinl has received compensations from TEVA and Novartis. E. Meinl and M. Krumbholz have received grant support from Novartis.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Institute of Clinical NeuroimmunologyLudwig Maximilian University of MunichMunichGermany

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