Loss of STAT6 promotes autoimmune disease and atopy on a susceptible genetic background

► Deficiency of the Th2 transcription factor STAT6 can promote atopy and autoimmunity. ► Loss of STAT6 markedly exacerbates autoimmune disease in Lyn−/− mice. ► Aged Lyn−/−STAT6−/− mice produce autoreactive IgE. ► Older Lyn−/−STAT6−/− mice have dramatically increased IgE but minimal IgG1. ► STAT6-independent factors can promote IgE class-switching in the absence of IgG1.