Differential H-2 antigen expression in teratocarcinoma-fibroblast hybrids.
Embryo-derived teratocarcinoma cells, like early embryonic cells, do not express the classical MHC class I antigens. The mRNAs for both the H-2 alpha chain and beta2-microglobulin are also undetectable in these cells. We observed that upon fusion of H-2-negative mouse P19 teratocarcinoma cells (H-2k allotype) with H-2-positive embryonic fibroblasts of C57BL/6 origin (H-2b allotype), teratocarcinoma-like cell hybrids were obtained which express the H-2Kb antigen derived from the embryonic fibroblasts, but not the H-2KkDk antigens of the teratocarcinoma. This finding demonstrates that the teratocarcinoma H-2 genes do not respond to the positive regulatory factors present in the hybrids. The H-2k allele was not lost during fusion, as shown by its expression in retinoic-acid-differentiated hybrids treated with interferon-gamma (10 U/ml, 4 days). H-2KkDk antigen expression could also be induced in the undifferentiated hybrids by treating the cells with the protein synthesis inhibitor cycloheximide (1-10 mu g/ml, 18 h), but not with the demethylating agent 5-azacytidine (5 mu M, 2-4 days). These data suggest the presence of a labile, negative regulating protein factor which selectively prevents the expression of the teratocarcinoma-derived H-2 antigens. When the level of this factor(s) is reduced, the teratocarcinoma H-2 genes are capable of responding to the positive regulatory factors.
Sionov
R V
RV
The Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, The Hebrew University, Jerusalem, Israel.
Gallily
R
R
D000818:Animals; D000951:Antigens, Neoplasm / Q000187:drug effects / Q000235:genetics*; D001374:Azacitidine / Q000494:pharmacology; D002459:Cell Fusion / Q000187:drug effects / Q000276:immunology; D003513:Cycloheximide / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D006183:H-2 Antigens / Q000187:drug effects / Q000235:genetics*; D006825:Hybridomas / Q000737:chemistry / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018243:Teratocarcinoma / Q000235:genetics* / Q000276:immunology*
D000951:Antigens, Neoplasm; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007371:Interferon-gamma; D003513:Cycloheximide; D001374:Azacitidine