The role of B cells in multiple sclerosis: rationale for B-cell-targeted therapies

Abstract

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system with no clear etiology. Until recently, most studies have emphasized the role of T cells in the pathogenesis of multiple sclerosis. Data suggesting that B cells play a role in the pathogenesis of multiple sclerosis have been accumulating for the past five decades, demonstrating that the cerebrospinal fluid and central nervous system tissues of multiple sclerosis patients contain B cells, plasma cells, antibodies, and immunoglobulins. Data suggest that B cells are involved in antigen capture and presentation to T cells, cytokine production, antibody secretion, demyelination, tissue damage, and remyelination in multiple sclerosis. These advances in the understanding of B-cell and antibody roles in the pathophysiology of multiple sclerosis provide a strong rationale for B-cell-targeted therapies.

Cutting Edge: Importance of IL-6 and Cooperation between Innate and Adaptive Immune Receptors in Cellular Vaccination with B Lymphocytes

“…B cells have been implicated in multiple sclerosis through the direct enhancement of T cell responses in the absence of Ab production (20,21). In infectious diseases such as AIDS and bacterial meningitis, B cells have been shown to be important as innate immune cells, again independent of Ab production (22,23).…”

Chemotherapeutics in the treatment of multiple sclerosis

“…These activated cells then infiltrate the CNS by crossing the bloodbrain barrier (BBB) and thereafter release a variety of proinflammatory cytokines [Noseworthy et al 2000;van Boxel-Dezaire et al 1999;Yong et al 1998;Arnason et al 1996]. The release of proinflammatory cytokines is associated with a decrease in anti-inflammatory processes [van Boxel-Dezaire et al 1999], an increase in the secretion of toxic free radicals and increased oxidative stress [Gonsette, 2008;Rejdak et al 2008;Platten and Steinman, 2005], and the recruitment of macrophages and certain B cells [Racke, 2008;Noseworthy et al 2000]. These various processes lead to localized areas of demyelination, and oligodendrocyte and axonal loss [Noseworthy et al 2000].…”

Central nervous system inflammatory demyelination after rituximab therapy for idiopathic thrombocytopenic purpura

“…However, accumulating evidence supports the involvement of B cells, plasma cells, and immunoglobulins in CNS inflammatory diseases [22,23], and provides a strong rationale for B cell-targeted treatment for these disorders. Physicians should be aware that B cell ablative therapy seemingly has the rare potential to trigger or exacerbate CNS inflammatory demyelinating disease.…”