Roles of immunoglobulins and B cells in multiple sclerosis: from pathogenesis to treatment

Abstract

Immunoglobulins (Igs) have long been implicated in contributing to the disease course of multiple sclerosis (MS). The earliest and perhaps still most consistent abnormal immunologic laboratory finding in MS is the increased concentration of Ig in the CSF, representing intrathecal antibody synthesis. Analysis of CSF Ig in terms of rate of production and restricted diversity (oligoclonal bands) remains a supportive diagnostic criteria for MS. Despite large-scale studies such as the analysis of 1000 cases reported by Ebers and Paty [Ebers, G.C., Paty, D.W., 1980. CSF electrophoresis in one thousand patients. Can. J. Neurol. Sci. 7 (4) 275-280], the challenge of correlating CSF Ig profiles and specific disease phenotypes remains. More recently, evidence from animal models and several human studies suggests that antibody-independent functions of B cells may also be implicated in the pathogenesis of MS. This presentation considers what roles Ig and/or B cells can play in mediating or regulating disease-relevant immune responses in MS. A timely corollary is whether B cell/Ig-directed therapeutic strategies can be effective in MS.