Presence of Pancreatic Hormones in Islet Cells With MHC-Class II Antigen Expression

Abstract

In the normal rat pancreas, only few islet cells express MHC-class II antigens. Their nature and function has not yet been elucidated. We report a method for the purification of Ia-positive islet cells by fluorescence-activated cell sorting. The isolated mononuclear cells appear of nonendocrine origin but contain vacuoles with partially digested secretory vesicles. Both insulin- and glucagon-immunoreactive granules were identified in these vacuoles of varying size and composition. It is suggested that at least part of the rat islet cells with class II antigen expression can exhibit phagocytotic properties leading to the uptake of fragments from damaged endocrine cells. This functional characteristic may implicate this particular islet cell type in the pathology of the endocrine pancreas in type I diabetes.

The biosociology of pancreatic B cells

“…The existence of macrophages in normal islet tissue was already previously suggested [53][54][55]. Our observations have demonstrated that these cells may exhibit the capability to incorporate fragments of damaged B cells [52]. Additional cell markers may thus become necessary to distinguish, in pancreatic sections, insulin-containing myeloid cells from pancreatic B cells with induced MHC-class II expression, in particular since both cell types can be associated to processes of B-cell destruction [56,57].…”

“…They are to be distinguished from other islet cells which contain small but distinct accumulations of insulin-immunoreactive material. The latter cell type was recognised in the Ia-positive islet cell population after its isolation by fluorescence-activated cell sorting [52]. Approximately 50 percent of the Ia-positive islet cells stained positively for insulin (Fig.…”

“…7). Insulin immunoreactive material was also detected in electron micrographs of Ia-positive islet cells, where it was located in vacuoles of varying size and electron density [52]. The insulin-containing cells with Ia expression lacked the ultrastructural characteristics of endocrine cells, but rather corresponded to myeloid cells with macrophagic properties [52].…”

“…It was therefore tested whether newly formed aggregates which are exclusively composed of Ia-negative islet cells can be transplanted across a major histocompatibility barrier. Our experiments were conducted in streptozotocin-diabetic rats, and used fluorescence-activated cell sorting to eliminate Ia-expressing cells from the donor cell preparation [52]. Aggregates composed of Ia-negative islet cells were rejected within 3 weeks after transplantation (Table 5, [94][95][96]).…”

In situ analysis of pancreatic islets in rats developing diabetes. Appearance of nonendocrine cells with surface MHC class II antigens and cytoplasmic insulin immunoreactivity.

“…However, the identification of these MHC class II positive cells as endocrine cells occurred only by light microscopy, leaving the theoretical possibility that they may also correspond to nonendocrine cells that occur superimposed with endocrine cells or have ingested or engulfed remnants of endocrine cells. We became particularly interested in the latter possibility after we had observed the presence of insulin-immunoreactive material in isolated nonendocrine islet cells with MHC class II antigen expression (5). In the present study, we examined whether insulin-containing nonendocrine cells can occur in vivo and whether their appearance is related to the destruction of pancreatic B cells.…”