Overproduction and secretion of β2-microglobulin by a rat thymic epithelial cell line that expresses MHC class I heavy chain

Abstract

Major histocompatibility complex (MHC) class I antigens are constituted of dimers consisting of a peripheral light chain, β2-microglobulin (β2m) and a transmembrane heavy chain whose cell surface expression depends on its assembly with β2m. In contrast, soluble β2m can be secreted in the absence of heavy chain expression. The presence of β2m in medium conditioned by a rat thymic epithelial cell line, IT45-R1 (IT45) prompted us to investigate whether β2m could be secreted by cells that express MHC class I antigens. IT45 cells produce three to five times more β2m in the culture supernatant than another rat thymic epithelial cell line, IT26-R21 (IT26). The IT45 cell line exported β2m through a constitutive pathway of secretion, as indicated by the kinetics of production and localization of intracellular β2m. Although cells from the IT45 cell line expressed a much higher amount of β2m as compared to IT26 and NBT II cells (a rat bladder epithelial cell line), all three of these cell lines expressed the same amount of membrane and intracellular MHC class I heavy chain. These data are thus consistent with a constitutive secretion of β2m dependent upon an overexpression of MHC class I light chain as compared to the heavy chain. The amount of β2m mRNA and the ratio of β2m versus MHC class I heavy chain transcripts were higher in IT45 than in IT26 cells, indicating that overexpression of β2m in IT45 cells could be due to an enhanced level of β2m mRNA. These results demonstrate that β2m can be oversynthezised and consequently secreted by cells that express MHC class I heavy chains. It may thus suggest that β2m could be secreted differentialy at specific body sites, which remain to be determined.