B cells are multifunctional players in multiple sclerosis pathogenesis: insights from therapeutic interventions

• Main Authors: Nele eClaes, Judith eFraussen, Piet eStinissen, Raymond eHupperts, Veerle eSomers
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2015-12-01
• Series: Frontiers in Immunology
• Subjects: Antibodies; Antigen Presentation; Cytokines; Multiple Sclerosis; therapy; costimulation
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00642/full

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.