Autoreactive antibodies control blood glucose by regulating insulin homeostasis
Timm Amendt, Gabriele Allies, Antonella Nicolò, Omar El Ayoubi, Marc Young, Tamás Rőszer, Corinna S. Setz, Klaus Warnatz, Hassan Jumaa
Abstract
Significance The random nature of antibody repertoire generation includes the potential of producing autoantibodies recognizing self-structures. It is believed that establishing immunological tolerance and prevention of autoimmune diseases require the removal of antibody specificities recognizing self. Using insulin as a common and physiologically important autoantigen, we show that anti-insulin antibodies associated with autoimmune diabetes can readily be detected in mice and humans and are involved in the physiological regulation of blood glucose levels. Importantly, human high-affinity, anti-insulin IgM antibodies protect insulin from autoimmune degradation by anti-insulin IgG antibodies. Thus, in contrast to the proposed negative selection, self-recognition and the production of highly autoreactive IgM antibodies are important for tolerance induction.