Studies on Autoimmunity for Initiation of β-Cell Destruction: VII. Evidence for Antigenic Changes on β-Cells Leading to Autoimmune Destruction of β-Cells in BB Rats

Abstract

The diabetic syndrome in BioBreeding (BB) rats is believed to result from the destruction of β-cells by autoimmune responses. However, the initial events that cause the autoimmune destruction of β-cells remain largely unknown. This investigation was initiated to see whether there are any antigenic changes on the β-cells from neonatal to adult BB rats that may lead to the autoimmune destruction of β-cells. Pancreatic grafts from neonatal BB rats remained largely intact without insulitis when transplanted into the renal subcapsular space of acutely diabetic BB rats. Similarly transplanted islet grafts from neonatal BB rats were also not subject to autoimmune destruction. In contrast, islet grafts obtained from adult BB rats, which had been treated with silica to prevent insulitis, were rapidly destroyed in diabetic recipients. These results indicate that β-cells from neonatal BB rats are different from β-cells from adult BB rats, at least regarding their recognition by immunologic effectors. Considering our observations and previous information on the initial role of macrophages/dendritic cells in the development of insulitis in BB rats, we suggest that β-cell–specific antigenic changes that precede insulitis may result in the autoimmune destruction of β-cells in BB rats.