IFN-? treatment requires B cells for efficacy in neuroautoimmunity.

ABSTRACT: IFN-? remains the most widely prescribed treatment for relapsing remitting multiple sclerosis. Despite widespread use of IFN-?, the therapeutic mechanism is still partially understood. Particularly, the clinical relevance of increased B cell activity during IFN-? treatment is unclear. In this article, we show that IFN-? pushes some B cells into a transitional, regulatory population that is a critical mechanism for therapy. IFN-? treatment increases the absolute number of regulatory CD19(+)CD24(++)CD38(++) transitional B cells in peripheral blood relative to treatment-naive and Copaxone-treated patients. In addition, we found that transitional B cells from both healthy controls and IFN-?-treated MS patients are potent producers of IL-10, and that the capability of IFN-? to induce IL-10 is amplified when B cells are stimulated. Similar changes are seen in mice with experimental autoimmune encephalomyelitis. IFN-? treatment increases transitional and regulatory B cell populations, as well as IL-10 secretion in the spleen. Furthermore, we found that IFN-? increases autoantibody production, implicating humoral immune activation in B cell regulatory responses. Finally, we demonstrate that IFN-? therapy requires immune-regulatory B cells by showing that B cell-deficient mice do not benefit clinically or histopathologically from IFN-? treatment. These results have significant implications for the diagnosis and treatment of relapsing remitting multiple sclerosis.

SUBMITTER: Schubert RD 

PROVIDER: S-EPMC4340715 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature