ACTIVE SUPPRESSION OF THE CLASS-II TRANSACTIVATOR-ENCODING AIR-1 LOCUS IS RESPONSIBLE FOR THE LACK OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II GENE-EXPRESSION OBSERVED DURING DIFFERENTIATION FROM B-CELLS TO PLASMA-CELLS

In this study the genetic control of major histocompatibility complex (MHC) class II gene expression during the transition from B cell to pl asma cell has been analyzed. Class LI molecules are not expressed in p lasma cells because of an active suppression resulting in the abrogati on of class II gene transcription. We show here that the plasma cell-s pecific repressor function, designated SIR (suppressor of immune respo nse genes), does not act directly on the transcription of class II gen es, but instead on the transcription of the AIR-1 gene, whose product, the class II transactivator (CIITA), is fundamental for tile regulati on of the constitutive and inducible expression of MHC class II genes. This was unambiguously demonstrated by the fact that plasmacytoma x B cell hybrids carrying an AIR-1 locus derived from CIITA-expressing ce lls do not express CIITA-specific transcripts. Transfection of a cDNA containing the human CIITA coding sequence under the control of an het erologous promoter restores expression of human MHC class II genes in the hybrids and is responsible for ne novo expression of mouse MWC cla ss II genes in both the mouse plasmacytoma cell line and the hybrids. These results confirm and extend the notion of the functional conserva tion of the AIR-1 gene product across species barriers. Interestingly, in CIITA-transfected cell hybrids, cell surface expression of the hum an HLA-DQ heterodimer was not observed. This result was not attributab le to lack of HLA-DQ alpha or -DQ beta transcription, because both tra nscripts were present in the CIITA-transfected hybrids, although at re duced levels, These findings further support our previous observations on the distinct regulation of expression of the human HLA-DQ class IT subset, which may be thus controlled at the post-transcriptional leve l by a CIITA-independent mechanism.