Differential expression and regulation of a human transgene, HLA-B27, in mouse placental and embryonic cell lines.
Unlike other somatic cells, human placental trophoblast cells do not express the highly polymorphic HLA-A and HLA-B human leukocyte major histocompatibility antigens that would stimulate maternal immunological rejection of the fetus. To investigate mechanisms underlying cell lineage-specific expression, cell lines were generated from homozygous matings of HLA-B27 transgenic mice. Trophoblast cell lines were generated from gestation day 10 placentas and fibroblasts were cultured from gestation day 13/14 embryos. Polymerase chain reaction (PCR) readily identified HLA-B DNA in transgenic trophoblastic cells but specific mRNA was of low abundance, being detectable by reverse transcriptase PCR but not by Northern blot hybridization. HLA-B-specific protein in/on the trophoblast cells was undetectable by cell enzyme-linked immunosorbent assay and the protein was not induced by exposing the trophoblastic cells to interferon-gamma (IFN-gamma). Restricted expression was specific for the HLA-B transgene and its antigen; IFN-gamma-inducible endogenous H-2Db class I antigens were detectable on the trophoblast cells. In contrast to the trophoblastic cells, HLA-B27 transgenic fibroblasts expressed IFN-gamma-inducible HLA class I antigens as well as H-2Db antigens. Thus, the mechanism(s) regulating expression of the polymorphic HLA-B antigen in trophoblastic cells is gene-specific, IFN-gamma-resistant and operative at the level of transcription or immediate post-transcription.
Hunt
J S
JS
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66160-7400, USA.
Banerjee
S
S
Pace
J L
JL
D000818:Animals; D002460:Cell Line; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006183:H-2 Antigens / Q000187:drug effects / Q000378:metabolism; D015796:HLA-B27 Antigen / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D006720:Homozygote; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger; D019076:Transgenes; D014327:Trophoblasts / Q000378:metabolism
D006183:H-2 Antigens; D015796:HLA-B27 Antigen; D064532:Histocompatibility Antigen H-2D; D012333:RNA, Messenger; D007371:Interferon-gamma