Intracisternal Type A particles in murine pancreatic B cells. Immunocytochemical demonstration of increased antigen (p73) in genetically diabetic mice.

Intracisternal Type A particles (IAPs) are retroviruslike structures identified by a core protein antigen (p73) and found in mouse embryos, in many mouse tumor cells, and in pancreatic B cells of some strains of genetically diabetic mice. Using both peroxidase-antiperoxidase and protein A-gold immunocytochemical techniques to localize p73, the authors have observed differences in intracellular antigen distribution between MOPC-104E, a mouse tumor cell line rich in IAP, and B cells from genetically diabetic (db/db) mice of the CBA/LtJ and C57BL/KsJ strain. In MOPC-104E cells studied by electron microscopy, localization of protein A-gold complex label was almost exclusively limited to IAP and their sites of assembly on the rough endoplasmic reticulum. In contrast, p73 appeared widely distributed throughout the cytoplasm of B cells from hyperglycemic db/db mice but not normal littermate controls. In addition to distribution over budding IAP, label was also found dispersed through other cytoplasmic organelles involved in secretion, including Golgi complexes and secretory granules. Patch labeling of B cell surfaces was sometimes observed. An ultrastructural survey of islets isolated from normal mice of 7 inbred genetic backgrounds on which the "diabetes" (db) gene has been studied showed that constitutive ability to produce IAP was associated with strain susceptibility to severe diabetes (eg, C57BL/KsJ, DBA/2J, CBA/LtJ, and C3HeB/FeJ). Strains whose B cells failed to show constitutive expression in situ or glucose-inducible expression in cell culture were resistant to the diabetogenic action of db genes. The possibility is discussed that p73 may represent a "neoantigen" which sensitizes the diabetic mouse to reject, by autoimmune mechanisms, the B cells expressing it.