Abstract
B cells, plasma cells and antibodies may play a key role in the pathogenesis of multiple sclerosis (MS). This notion is supported by various immunological changes observed in MS patients, such as activation and pro-inflammatory differentiation of peripheral blood B cells, the persistence of clonally expanded plasma cells producing immunoglobulins in the cerebrospinal fluid, as well as the composition of inflammatory central nervous system lesions frequently containing co-localizing antibody depositions and activated complement. In recent years, the perception of a respective pathophysiological B cell involvement was vividly promoted by the empirical success of anti-CD20-mediated B cell depletion in clinical trials; based on these findings, the first monoclonal anti-CD20 antibody—ocrelizumab—is currently in the process of being approved for treatment of MS. In this review, we summarize the current knowledge on the role of B cells, plasma cells and antibodies in MS and elucidate how approved and future treatments, first and foremost anti-CD20 antibodies, therapeutically modify these B cell components. We will furthermore describe regulatory functions of B cells in MS and discuss how the evolving knowledge of these therapeutically desirable B cell properties can be harnessed to improve future safety and efficacy of B cell-directed therapy in MS.
Highlights
IntroductionB cells and their products gained enormous interest in multiple sclerosis (MS)
Within the last decade, B cells and their products gained enormous interest in multiple sclerosis (MS)
In light of the constantly increasing number of powerful therapeutic alternatives [139], it will be essential to develop biomarkers indicative of pathogenic B cell function in an individual patient prior to initiation of therapy. It is largely unknown how often and how long a patient with MS, neuromyelitis optica (NMO) or NMO-spectrum disorder (NMO-SD) should be depleted of peripheral B cells
Summary
B cells and their products gained enormous interest in multiple sclerosis (MS). In light of the rapid clinical benefit, these trials established an important cellular B cell function independent of antibody production. We will highlight current knowledge of the role of B cells, plasma cells and antibodies in the development and progression of MS. Within this first section, we will describe how activated B cells may contribute to MS pathogenesis as the source of antibody-producing plasma cells, potent antigen presenting cells (APC) and providers of pro-inflammatory cytokines, and how the developing inflammatory CNS milieu may unfavorably foster pathogenic B cell function locally. We will elucidate how the clinical trial findings feed-back on the theoretical concept on the role of B cells in MS and forecast how both fields, increasing immunological knowledge on the diverse role of B cells and empiric success of B cell-directed therapy can merge to incite our ambition to further improve B cell-directed therapy in MS
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