Antibody-Independent Functions of B cells in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervoussystem (CNS). Various pro-inflammatory immune cells mediate local pathology. CD20 depletion therapies and genome-wide association studies (GWAS) have shown that the contribution of B cells to the pathogenesis of MS is indisputable. The strong and rapid beneficial clinical effects of anti-CD20 treatment in MS patients has revealed that B cells serve as antigen-presenting rather than antibody-producing cells in the periphery. Although pro-inflammatory Th-cell responses are significantly reduced in these patients, the exact underlying antibody-independent functions of B cells in MS are poorly understood. B cells activate TH cells through the presentation of antigens, expression of costimulatory molecules and secretion of cytokines. In this thesis, we aimed to uncover genes and pathways that are functionally altered in human B cells and potentially contribute to MS. To study this, we made use of gene silencing and functional assays related to B- and Th-cell interaction and took advantage of recent GWAS data, different MS cohorts and the effects of immunosuppressive conditions and treatment on disease activity