Sequential activation and loss of the pre-B cell Thy-1 gene in T-cell X pre-B cell somatic hybrids.
In somatic cell hybrids between the pseudodiploid Thy-1- Abelson-leukemia-virus-induced pre-B cell lymphoma RAW 253.1 and the Thy-1+ T-cell lymphoma, AKR1 (Thy-1+), all cells express the Thy-1 allele of the T-cell parent but most hybrid cells do not express the Thy-1 allele of the pre-B cell lymphoma parent. The Thy-1 allele of the pre-B cell parent, however, is spontaneously activated in a minor proportion of hybrid cells. By sorting for cells expressing the Thy-1 allele of the pre-B cell parent, derivative clones in which 100% of cells express both parental Thy-1 alleles can be isolated. Revertants with a phenotype identical with that of the original hybrid cell line can be isolated from these derivatives by sorting for nonexpression of the Thy-1 allele of the pre-B cell parent. These first-generation revertant cell lines have lost one copy of the Thy-1 gene derived from the pre-B cell lymphoma parent. By a further cycle of sorting, derivatives in which 100% of cells express both parental Thy-1 alleles can again be obtained. Second-generation revertants isolated by sorting these Thy-1+ hybrid cells for nonexpression of the Thy-1 allele of the pre-B cell parent no longer contain a normal copy of the pre-B cell Thy-1 allele and this surface antigen is no longer expressed by any cells in the population. These results are consistent with a mechanism that sequentially activates each copy of the Thy-1 gene derived from the pre-B cell lymphoma parent. Hybrids between the class D Thy-1- mutant, AKR1 (Thy-1- d), in which the 5' region of the Thy-1 structural gene has been deleted, and RAW 253.1 cannot be activated to express either Thy-1 allele. This result indicates that a sequence upstream of exon 2 of the active Thy-1 allele is critical for the initial activation event.
D000011:Abelson murine leukemia virus; D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000032:analysis; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006822:Hybrid Cells / Q000276:immunology*; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology; D018800:Thy-1 Antigens; D014407:Tumor Cells, Cultured / Q000276:immunology
D000954:Antigens, Surface; D018800:Thy-1 Antigens; D004247:DNA