Previous studies in this project have identified the intracisternal A-particle (IAP) genes as a genetically unique type retrovirous-like element extensively reiterated in the genomes of mice and some other rodent species. The past year has been a surprising development in which IAP genes have been linked to a class of soluble immunoregulatory molecules that can potentiate or suppress Ig production in target B cells. Drs. K Moore and K. Ishizaka succeeded in obtaining a cDNA clone which coded for 2 related polypeptides that enhanced production of IgE in mouse B-cells in vitro. Comparison of thier nucleotide sequence with that obtained in our laboratory for and authentic endogenous IAP gene firmly established that the cDNA represented a modified IAP element coding for type of gag-pol fusion protein. Antiserum previously prepared by us against purified IAP strucutural proteins was shown to bind the active immunoregulatory polypeptides produced both by the cDNA clone and by normal I-lymphocytes. In a continuing study with Dr. E. Leiter, on the possible role of IAP antigen expression in pathogenesis of insulin-dependent diabetes in mice, we have shown that IAP mRNA and proteins were induced in isolated pancreatic islets incubated in a high glucose medium and that both the basal and glucose-induced levels were significantly higher in islets from normal mice susceptible to the diabetogenic action of the db gene than in those from resistant strains. We postulate that beta cells carrying IAP-related antigen(s) on their cell surface may be subject to autoimmune attack.
