BB/E rats spontaneously develop a form of autoimmune diabetes resembling insulin-dependent diabetes mellitus (IDDM) in humans. IDDM results from central destruction of the insulin-producing β-cells of the pancreatic islets. Herein, we report that the outbreak of IDDM in BB/E rats is preceded by the spontaneous development of an anti-idiotypic antibody to a particular antibody to insulin made by the rats. This anti-idiotype, designated anti-DM-id, behaves as an antibody to the insulin-hormone receptor. Thus, a spontaneous anti-idiotypic antibody network whose products can affect the peripheral utilization of insulin seems to accompany the central destruction of β-cells in developing IDDM.

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