FasL-expressing B cells are major players in type 1 diabetes (BA6P.129)

Abstract

Abstract B cells serve both pathogenic and regulatory roles in Type 1 diabetes (T1D). Whereas the regulatory role is mainly limited to IL-10-producing (IL-10pos) B cells, little is known about the characteristics of pathogenic B cells. Here we identified a novel population of FasLhiCD5+ B cells that is significantly increased in T1D as compared to non-diabetic autoantibody positive (Ab+) subjects. Both the FasLhi and IL-10pos sets are localized within the CD5+ B subpopulation. However, FasLhiCD5+ B cells were significantly expanded and IL-10posCD5+ B cells decreased in T1D as compared to Ab+ subjects. FasLhiCD5+ B cells do not produce IL-10 and are largely spared from activation-induced apoptosis, whereas IL-10posCD5+ B cells are prone to Fas-mediated apoptosis. Causally, using NOD mouse model, we identified FasL-expressing B cells as negative regulators of IL-10pos B cells and facilitators of islet infiltration by diabetogenic T cells. These results identify FasLhiCD5+ B cells as an elevated subpopulation in T1D subjects and initiator of the diabetogenic process in NOD mice.