Divergent evolution in the mechanisms controlling MHC class II gene transcription in mouse and human.

The expression of the major histocompatibility complex (MHC) class II gene family is developmentally regulated and, in generaI, in a coordinate manner. In this study, we show that the expression of the entire repertoire of human class II genes, otherwise transcriptionally silent in the bare Iymphocyte syndrome derived BLSI celI line, can be rescued by somatic celI hybridization with normal mouse spleen celIs. The analysis of the interspecies celI hybrids revealed a particularly important and unprecedented aspect. A return to the BLSI-like, human MHC class Il-negative phenotype due to segregation of mouse chromosomes was accompanied in certain hybrids by loss of lE, but not lA cell surface antigen expression. At the molecular level, this was the result of lack of Ea-specific mRNA in the presence of E beta-, A alpha- and A beta- specific mRNA. Thus, the mouse trans-acting function operating across species barriers and able to complement the defect of human BLSI cells diverged in mice to control Ea, but not Eb, Aa and Ab gene expression. These findings suggest that evolutionary pressure has maintained the expression of the MHC class II multigene family under the control of quite distinct species-specific transcriptionai mechanisms.