Immunosuppressive anti-immunoglobulin autoantibodies: specificity, gene structure and function in health and disease

Anti-immunoglobulin autoantibodies (anti-Ig auto-Abs) are part of the physiological immune repertoire. Herein we focus on Abs directed against the F(ab')2 region of the Ig molecule. The vast majority of previously described anti-F(ab')2 auto-Abs were antiidiotypes. The antibodies we studied recognize epitopes located in the hinge region of IgG and in other conserved domains of F(ab')2. Gene structure analyses revealed germline gene identity of VL chains and 88% homology with the closest germline gene of VH chains. We present evidence for a B cell suppressive role of anti-Ig Abs and discuss the mechanism of suppression. Moreover, the role of anti-Ig auto-Abs in immunoregulation as well as in the pathogenesis of autoimmune and other diseases is discussed. There is substantial evidence indicating that anti-Ig auto-Abs are important immunoregulatory molecules.