B-cell immunity in MS

Abstract

T-cell-mediated immunity has dominated studies of multiple sclerosis (MS) pathogenesis, mainly due to detection of activated T-cells in MS lesions, and analogies with the animal model experimental allergic encephalomyelitis. The prevailing aetiological hypothesis is that MS is a multifactorial disorder, affecting individuals predisposed by a combination of susceptibility genes and environmental factors. Plaque formation is attributed to immune mechanisms, triggered by an autoimmune attack directed against antigens in the myelin membrane. This article reviews the roles of components of the immune response in MS including B-cells, the complement cascade, antibodies and genes. Evidence suggests that B-cell clonal expansion in cerebrospinal fluid and plaques of MS patients indicate an ongoing, antigen-driven response in the central nervous system. That MS is an autoimmune disease remains inconclusive, but the assumption is that humoral immunity plays a role in lesion formation and perpetuation, or is involved in tissue-repair mechanisms. The paradigm of MS as a T-cell disease must be revisited, as B-cells are involved during the initial and later disease stages, and evidence is mounting for a 'degenerative process', in addition to (and possibly even preceding) inflammation.