B-cell function in CNS inflammatory demyelinating disease: a complexity of roles and a wealth of possibilities.
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.
Fillatreau
Simon
S
Immune Regulation Group, Deutsches Rheuma-Forschungszentrum, Chariteplatz 1, 10117 Berlin, Germany. fillatreau@drfz.de
Anderton
Stephen M
SM