Localization of beta 2-microglobulin in the term villous syncytiotrophoblast.
The non-covalent association of beta 2-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 beta 2-microglobulin synthesis and localization in the term villous syncytiotrophoblast were contradictory, we investigated the subcellular localization of beta 2-microglobulin by immunoelectron microscopy. Synthesis in the trophoblast is demonstrated by colocalization of beta 2-microglobulin with protein disulfide isomerase, a marker protein of the endoplasmic reticulum. The presence of beta 2-microglobulin at the apical plasma membrane corresponds to the recently observed association of beta 2-microglobulin with HFE and FcRn. Localization of beta 2-microglobulin in late endosomes/lysosomes, labeled with antibodies to lysosome membrane antigen LAMP 2, suggests also a degradative route of beta 2-microglobulin internalized by fluid-phase from the maternal blood.
Leitner
Karl
K
Department of Pathophysiology, University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Ellinger
Adolf
A
Zimmer
Klaus-Peter
KP
Ellinger
Isabella
I
Fuchs
Renate
R
D015703:Antigens, CD / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D010920:Placenta / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D014327:Trophoblasts / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D001613:beta 2-Microglobulin / Q000032:analysis* / Q000378:metabolism
D015703:Antigens, CD; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D011990:Receptors, Transferrin; D001613:beta 2-Microglobulin; D019704:Protein Disulfide-Isomerases