IgG-positive cells surround pancreatic ducts and form multiple layers after streptozotocin treatment

Abstract

Although numerous studies of diabetes have focused on cell-mediated immunity to pancreatic islet cells, little is known about immune cells in the pancreatic duct region. In this study, we found that membrane immunoglobulin G (IgG)-positive cells comprised about 1.4% of the total pancreatic cells in mice, forming a thin septum that surrounds large and medium pancreatic ducts. The IgG-positive cells showed low expression of beta-catenin and were amylase-, cytokeratin-, insulin-, and glucagon-negative. Flow cytometric analysis showed that the IgG-positive cells were also positive for CD45, Sca-1, c-Kit, CD49f, and CD133, and negative for Flk-1, suggesting that they were undifferentiated hematopoietic cells. On day 5 after streptozotocin treatment, the percentage of periductal IgG-positive cells increased to 3.37% of total pancreatic cells, and the periductal IgG-positive cells formed multiple layers (beta-catenin-low, and amylase-, cytokeratin-, insulin-, glucagon-negative). These cells were Ki67-negative, suggesting they were recruited from hematopoietic cells. We further found that IgG-positive cells formed multiple layers around large ducts of pancreas from NOD mice. Our findings reveal the existence of periductal IgG-positive cells in the adult mouse pancreas, which were activated during streptozotocin-induced diabetes, adding a new dimension to our understanding of immunity in diabetes.