Reactivation by a trans-acting factor of human major histocompatibility complex Ia gene expression in interspecies hybrids between an Ia-negative human B-cell variant and an Ia-positive mouse B-cell lymphoma.

Raji, a human B-lymphoma cell line, expresses high levels of class II (Ia) antigens. The expression of Ia antigens is totally abolished at the level of specific mRNA accumulation in RJ 2.2.5, a variant cell line derived from Raji after mutagenesis and immunoselection. We report here that the human Ia antigen expression can be restored in interspecies somatic cell hybrids between RJ 2.2.5 cells and BALB/c-derived M12.4.1 (I-A+, I-E+) B-lymphoma cells. Two hybrid clones were studied in detail. In both clones Ia molecules of the DR and NG2 type were easily detected by cell surface immunofluorescence and specific immunoprecipitation. In contrast, the DQ1 molecules were not detected with the above technique. DNA hybridization experiments using specific probes indicated that alpha-chain DR and beta-chain DQ genes were present in the hybrids. However, RNA hybridization experiments revealed that beta-chain DQ mRNA was present in the hybrids at very low amount compared to alpha-chain DR-specific mRNA. These results indicate that at least several genes of the class II gene cluster are coordinately regulated by trans-acting factor(s) that operate across species barriers. The basis of the mechanisms controlling the expression of class II antigens in these human-mouse hybrids might be related to the extinction (lack of expression) or activation of tissue-specific traits that take place when genomes of cells of dissimilar developmental potentials are brought together.