B-cell function in CNS inflammatory demyelinating disease: a complexity of roles and a wealth of possibilities

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.

Keywords::

• antibody
• autoimmunity
• B cell
• experimental autoimmune encephalomyelitis
• IL-10
• immune tolerance
• multiple sclerosis

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.