This chapter provides an overview of treatments targeting B-cells and humoral responses in multiple sclerosis (MS). Intravenous Ig (IVIg) and plasma exchange (PLEX) action provide successful treatment of active MS relapses or prevention of relapses. Rituximab has been evaluated for its potential to treat autoimmune states in which B-cells and autoantibodies have been thought to contribute to disease pathophysiology. Ocrelizumab is a humanized anti-CD20 monoclonal antibody (IgG1) that recognizes an epitope that overlaps with that recognized by rituximab. Ofatumumab targets an epitope different from rituximab and most other anti-CD20 antibodies. The initial pursuit of clinical trials with rituximab in MS was based on the consideration that such an approach would serve to decrease precursors to plasma cells, thereby reducing synthesis of potentially pathogenic central nervous system (CNS)-directed antibodies. The success of B-cell depletion in MS has opened the door to a therapeutic strategy.

This chapter focuses on how the immune system is thought to contribute to the multiple sclerosis (MS) process through the different disease phases, including initiation and propagation, and in different anatomical compartments. Several subsets of regulatory T-cells are capable of inhibiting activation of other T-cells, including suppression of autoimmune responses. Clinical trials of B-cell depletion with rituximab and more recently ocrelizumab have demonstrated substantial reductions in new brain lesions, and relapses in MS patients. The innate immune system rapidly senses foreign pathogen-associated structures without the need for adaptive antigen-specific recognition or memory responses. The presence of clonally expanded CD4 and CD8 T-cells persisting in the CNS, suggests that T-cells can be activated or re-activated within the central nervous system (CNS) compartment. Cellular immune responses and soluble factors can have protective and potentially growth permissive influences capable of limiting injury, as well as promoting survival and repair of neural elements.