MS and the B cell controversy

Anne H. Cross (1) , Emmanuelle Waubant (2)

1 Department of Neurology
2 Department of Neurology

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 has 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.

Mots clés: Multiple sclerosis; B lymphocytes; antibodies; rituximab; therapy

Anne H. Cross, Emmanuelle Waubant. MS and the B cell controversy. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2010, 1812 (2), pp.231. ⟨10.1016/j.bbadis.2010.07.020⟩. ⟨hal-00652657⟩