title: A case for regulatory B cells in controlling the severity of autoimmune-mediated inflammation in experimental autoimmune encephalomyelitis and multiple sclerosis.
abstract: Multiple sclerosis (MS) is considered to be a T cell-mediated autoimmune disease that results in the presence of inflammatory lesions/plaques associated with mononuclear cell infiltrates, demyelination and axonal damage within the central nervous system (CNS). To date, FDA approved therapies in MS are thought to largely function by modulation of the immune response. Since autoimmune responses require many arms of the immune system, the direct cellular mechanisms of action of MS therapeutics are not definitively known. The mouse model of MS, experimental autoimmune encephalomyelitis (EAE), has been instrumental in deciphering the mechanism of action of MS drugs. In addition, EAE has been widely used to study the contribution of individual components of the immune system in CNS autoimmunity. In this regard, the role of B cells in EAE has been studied in mice deficient in B cells due to genetic ablation and following depletion with a B cell-targeted monoclonal antibody (mAb) (anti-CD20). Both strategies have indicated that B cells regulate the extent of EAE clinical disease and in their absence disease is exacerbated. Thus a new population of "regulatory B cells" has emerged. One reoccurring component of regulatory B cell function is the production of IL-10, a pleiotropic cytokine with potent anti-inflammatory properties. B cell depletion has also indicated that B cells, in particular antibody production, play a pathogenic role in EAE. B cell depletion in MS using a mAb to CD20 (rituximab) has shown promising results. In this review, we will discuss the current thinking on the role of B cells in MS drawing from knowledge gained in EAE studies and clinical trials using therapeutics that target B cells.
authors.affiliation: BloodCenter of Wisconsin, Blood Research Institute, Milwaukee, WI, United States.
authors.forename: Avijit
authors.initials: A
authors.lastname: Ray
authors.forename: Monica K
authors.initials: MK
authors.lastname: Mann
authors.forename: Sreemanti
authors.initials: S
authors.lastname: Basu
authors.forename: Bonnie N
authors.initials: BN
authors.lastname: Dittel
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006801:Humans; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology*