Localization of β2-microglobulin in the term villous syncytiotrophoblast

Abstract.

The non-covalent association of β2-microglobulin with MHC class I molecules and MHC class I-type molecules such as FcRn or the hemochromatosis protein (HFE) is of major importance for their function, i.e., antigen presentation, IgG transport, and regulation of iron uptake, respectively. In the human hemochorial placenta, the syncytiotrophoblast forms a continuous epithelial layer covering the villous trees, where it directly contacts maternal blood and, among many other functions, mediates uptake of maternal IgG and iron. The villous syncytiotrophoblast lacks MHC class I molecules but expresses FcRn and HFE. Since data on β2-microglobulin synthesis and localization in the term villous syncytiotrophoblast were contradictory, we investigated the subcellular localization of β2-microglobulin by immunoelectron microscopy. Synthesis in the trophoblast is demonstrated by colocalization of β2-microglobulin with protein disulfide isomerase, a marker protein of the endoplasmic reticulum. The presence of β2-microglobulin at the apical plasma membrane corresponds to the recently observed association of β2-microglobulin with HFE and FcRn. Localization of β2-microglobulin in late endosomes/lysosomes, labeled with antibodies to lysosome membrane antigen LAMP 2, suggests also a degradative route of β2-microglobulin internalized by fluid-phase from the maternal blood.