Insights into the role of B cells in the cortical pathology of Multiple sclerosis: evidence from animal models and patients

Abstract

Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system (CNS) that affects both white and gray matter. Although it has been traditionally considered as a T cell mediated disease, the role of B cell in MS pathology has become a topic of great research interest. Cortical lesions, key feature of the progressive forms of MS, are involved in cognitive impairment and worsening of the patients’ outcome. These lesions present pathognomonic hallmarks, such as: absence of blood-brain barrier (BBB) disruption, limited inflammatory events, reactive microglia, neurodegeneration, demyelination and meningeal inflammation. B cells located in the meninges, either as part of diffuse inflammation or as part of follicle-like structures, are strongly associated with cortical damage. The function of CD20-expressing B cells in MS is further highlighted by the success of specific therapies using anti-CD20 antibodies. The possible roles of B cells in pathology go beyond their ability to produce antibodies, as they also present antigens to T cells, secrete cytokines (both pathogenic and protective) within the CNS to modulate T and myeloid cell functions, and are involved in meningeal inflammation. Here, we will review the contributions of B cells to the pathogenesis of meningeal inflammation and cortical lesions in MS patients as well as in preclinical animal models.