Human-mouse hybrids with an embryonal carcinoma phenotype continue to transcribe HLA-A,B,C

We previously constructed a hybrid cell line, MCP6, which contains an X/6 translocation chromosome as its sole human genetic component in a mouse embryonal carcinoma (EC) cell background. This chromosome, which carries the major histocompatibility complex (MHC) originated from a human B cell which expresses class I and class II MHC antigens. EC cells do not express class I or class II antigens on their cell surface. Northern blot analysis has now shown that in the MCP6 hybrid, human class I genes, i.e., HLA-A,B,C, continued to be transcribed, and cellular levels of the transcripts were similar to, or only slightly lower than, levels in hybrids with a non-EC phenotype. However, very low levels of mRNA species recognised by a mouse class I gene (H-2) probe were also detected in EC cells and EC hybrids. Comparison of the relative levels of H-2 and HLA class I gene transcripts in the EC hybrids and non-EC hybrids indicated that the introduced HLA-A,B,C genes were not appropriately regulated in the EC cell but were subject at least in part to cis control. In contrast to the class I genes, no class II gene (i.e. HLA-DR alpha) transcripts were detected in MCP6. Hybrid EC lines thus provide a system to investigate the different levels of control of MHC gene expression during development and may help to elucidate mechanisms whereby the embryonic genome programs expression of differentiated cell functions.