INSULIN-DEPENDENT DIABETES IN THE NOD MOUSE MODEL .1. DETECTION AND CHARACTERIZATION OF AUTOANTIBODY BOUND TO THE SURFACE OF PANCREATIC BETA-CELLS PRIOR TO DEVELOPMENT OF THE INSULITIS LESION IN PREDIABETIC NOD MICE

Type I, insulin-dependent diabetes (IDD) results from an autoimmune re sponse against the insulin producing pancreatic beta cells. This autoi mmune reaction involves both humoral and cell-mediated factors; nevert heless, the relative role of each remains unresolved. Furthermore, whi le adoptive transfer experiments have provided evidence for the role o f T cells in beta cell destruction, the specific events which initiate leukocyte migration into the islets (insulitis) are unknown. Earlier studies indicated that NOD pancreatic beta cells may bind small amount s of autoantibody. Because of the possible importance of an early humo ral response to the initiation of insulitis and subsequent disease, we have investigated a number of aspects of this phenomenon to determine the nature and specificity of the early autoantibodies as well as the time at which autoantibody binds to beta cells. Results of this study demonstrate that NOD/Uf mice are sensitized to islet-cell associated antigens, including GAD, prior to the first appearance of insulitis; t hat a small percentage of the beta cells of NOD/Uf mice have autoantib ody bound to their surface prior to insulitis; that sera collected fro m preinsulitis NOD/Uf mice contain autoantibodies which will bind to b eta cells of both IDD-prone and IDD-resistant mice; and that the autoa ntibodies which bind pancreatic beta cells are predominantly IgM with lesser amounts of IgG and IgA. These findings suggest that, in the nat ural course of IDD, insulitis may develop in response to an initial au toantibody-mediated injury of beta cells.