DIVERGENT EVOLUTION IN THE MECHANISMS CONTROLLING MAJOR HISTOCOMPATIBILITY COMPLEX 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 general, in a coordin ate manner. In this study, we show that the expression of the entire r epertoire of human class II genes, otherwise transcriptionally silent in the bare lymphocyte syndrome-derived BLS1 cell line, can be rescued by somatic cell hybridization with normal mouse spleen cells. The ana lysis of the interspecies cell hybrids revealed a particularly importa nt and unprecedented aspect. A return to the BLS1-like, human MHC clas s II-negative phenotype due to segregation of mouse chromosomes was ac companied in certain hybrids by loss of IE, but not IA cell surface an tigen expression. At the molecular level, this was the result of lack of E alpha-specific mRNA in the presence of E beta-. A alpha- and A be ta-specific mRNA. Thus, the mouse trans-acting function operating acro ss species barriers and able to complement the defect of human BLS1 ce lls diverged in mice to control Ea, bur not Eb, Aa and Ab gene express ion. 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 transcriptional mechanisms.