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.