PANCREATIC ISLET CELL SURFACE GLYCOPROTEINS CONTAINING Gall-4G1cNAc-R IDENTIFIED BY A CYTOTOXIC MONOCLONAL AUTOANTIBODY

The insulin-dependent diabetic syndromes of the BB rat and man have several characteristics in common that implicate autoimmune processes in the etiology of pancreatic a cell destruction . The main arguments in favor of this are early infiltration of the islets by mononuclear cells (1, 2), and the presence of islet cell cytoplasmic (ICA)' and surface autoantibodies (ICSA) (3). ICSA are immunocytochemically detectable in the sera ofpatients with recent onset insulin-dependent diabetes mellitus (IDDM) and also in newly diagnosed diabetic BB rats . In vitro, ICSA can be cytotoxic for a cells (4-6), suggesting that these circulating autoantibodies may be direct effectors of a cell destruction in IDDM . However, what role they actually play in causing islet cell damage is still not completely clear. From this point of view it would be of interest to characterize (3 cell-specific autoantigens recognized by ICSA. Efforts have been made to isolate autoantigens using patient sera (7, 8) and mAbs against islets (9-11) . In this study we describe the successful preparation by hybridoma technology of a complement-mediated cytotoxic monoclonal autoantibody from a diabetic BB rat that reacts with rat insulinoma cells (RINm5F) and primary rat islet cells . The functional properties of this antibody and the antigens to which it binds are defined.