IFN-ß Treatment Requires B Cells for Efficacy in Neuroautoimmunity. Journal of immunology Schubert, R. D., Hu, Y., Kumar, G., Szeto, S., Abraham, P., Winderl, J., Guthridge, J. M., Pardo, G., Dunn, J., Steinman, L., Axtell, R. C. 2015; 194 (5): 2110-2116


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

View details for DOI 10.4049/jimmunol.1402029

View details for PubMedID 25646307

View details for PubMedCentralID PMC4340715