B cells and autoantibodies in multiple sclerosis

Abstract

During the last decades, investigations into MS have centered predominantly on the pathogenic role of autoreactive T cells rather than B cells. Recently, more evidence for a role of the humoral immune response in the MS pathogenesis is provided by the efficiency of novel treatment strategies; the preliminary positive results of intravenous immunoglobulin (IVIG) and B cell targeting therapy (Rituximab) in a group of MS patients have led to a renewed focus on B cells and autoantibodies in this autoimmune disease. In this chapter, we describe the humoral immune response in MS. The B cell repertoire in healthy individuals and MS patients is discussed. Next, B cell functions in MS as well as B cell migration and survival in the central nervous system (CNS) are outlined. An overview is given of the evidence for the involvement of B cells in the pathogenesis of MS. Finally, different technologies for the study of the humoral reactivity profile in MS are described, including autoantibody profiling and B cell reactivity analysis. Phage display and B cell immortalization are described in more detail as examples of both reactivity screening approaches. The analysis of the reactivity profile of B cells and autoantibodies in MS is relevant for the identification of novel disease markers for diagnosis, prognosis and theranostics, as well as for the elucidation of the underlying disease processes to discover highly needed novel therapeutic targets for the disease.