NONTOLERANCE AND DIFFERENTIAL SUSCEPTIBILITY TO DIABETES IN TRANSGENIC MICE EXPRESSING MAJOR HISTOCOMPATIBILITY CLASS-II GENES ON PANCREATIC BETA-CELLS

In insulin‐dependent diabetes mellitus aberrant expression of major histocompatibility complex (MHC) class II antigens might induce autoimmune destruction of insulin‐producing pancreatic β cells. Here we demonstrate that already the expression of single MHC class II chains (Eαk and Eβb) is sufficient to cause diabetes without affecting β cell morphology and cell numbers. Our transgenes interfere at least in two points of insulin production leading to a severely diabetic phenotype. In one case Eβb expression led to a 10‐30‐fold decrease of mouse insulin mRNA. In another case Eαk expression reduced insulin secretion to background levels. In addition, we also found a patchy distribution of both insulin and Eαk expression, indicating heterogeneity of the β cell population, without the concommittant development of diabetes. Although the transgenic Eαk Eβb MHC class II molecules were expressed on the surface of pancreatic β cells, the transgenic mice did not prove to be tolerant for I‐E antigen. Autoimmune reactions remained absent showing that aberrant MHC class II expression on pancreatic β cells alone is not sufficient for the development of autoimmune diabetes in mice. Copyright © 1990 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim