MS and the B cell controversy.
The contribution of B cells and their products to the pathogenesis of MS has long been debated. The presence of B cells, plasma cells and excess immunoglobulins in MS lesions and in the cerebrospinal fluid of MS patients implicate the humoral immune system in the disease. Correlations of higher levels of CSF B cells and immunoglobulins found in some studies with a more aggressive clinical course of MS have bolstered the notion that the humoral immune system is involved in MS pathogenesis. However, until the advent of rituximab, a monoclonal antibody therapy that specifically lyses B cells, confirmation of the key role of B cells and their products in MS had been lacking. Development of this therapeutic monoclonal antibody to CD20, a cell surface molecule confined to B cells, allowed determination of the effects of B cell depletion. Perhaps somewhat unexpectedly, depletion of circulating B cells led to rapid and profound reduction in gadolinium enhancing lesions on brain MRI in three separate studies in relapsing MS subjects. When examined, depletion of B cells in the blood was accompanied by depletion of B cells in CSF. Notably, reduction of enhancing brain lesions was not accompanied by reduction in CSF immunoglobulins. Whether the critical role of B cells occurs in the periphery, in the CNS, or in both locations has not yet been determined.
Cross
Anne H
AH
Department of Neurology, Washington University School of Medicine, St. Louis, USA. crossa@neuro.wustl.edu
Waubant
Emmanuelle
E
D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001323:Autoantibodies / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002986:Clinical Trials as Topic; D006801:Humans; D008212:Lymphocyte Depletion; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D009103:Multiple Sclerosis / Q000209:etiology* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009185:Myelin Proteins / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology; D000069283:Rituximab
D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D009185:Myelin Proteins; D000069283:Rituximab