Abstract
Multiple sclerosis is a heterogeneous disease associated with a rupture of immunological tolerance toward CNS antigens in both T- and B-lymphocyte compartments. The association of human leukocyte antigen genes with higher susceptibility to multiple sclerosis, and the capacity of immune-modulating drugs that block leukocyte transit into the CNS (e.g., natalizumab) to limit pathogenesis confirms that immune cells play important roles in disease progression. An immune therapy that depletes B cells selectively (rituximab) is in clinical trials for multiple sclerosis. Experiments performed in the multiple sclerosis animal model of experimental autoimmune encephalomyelitis have highlighted multiple possible roles for B cells, ranging from being crucial for pathogenesis to being necessary for recovery from clinical disease. Thus, we may expect that patients in whom B cells are key players in the pathogenic process should benefit from rituximab, whereas those in whom B cells are involved predominantly in regulation may show disease exacerbation.
Acknowledgements
Work in Simon Fillatreau’s laboratory is funded by Deutsche Forschungsgemeinschaft, Association pour la Recherche sur la Sclerose en Plaques (ARSEP) and the Hertie Stiftung. Work in Stephen M Anderton’s laboratory is funded by the Medical Research Council (UK), the Wellcome Trust and the UK Multiple Sclerosis Society. Stephen M Anderton is a MRC Senior Research Fellow.