Revertants from the HLA class II regulatory mutant 6.1.6: implications for the regulation of Ia gene expression

Class II (Ia) genes of the human MHC code for developmentally regulated, highly polymorphic cell surface glycoproteins. The control of expression of this highly complex genetic region has not been extensively investigated. We used 6.1.6, a variant of a normal B lymphoblastoid cell that has lost expression of all class II molecules, to study this question. In previous studies, we have shown that the structural genes for class II molecules are intact but are not expressed in 6.1.6 (6), and that the defect is at the transcriptional level (7). In this report, we describe the isolation and characterization of revertants of 6.1.6 that reexpress class II molecules. These revertants have four unusual properties: 1) they are found at a higher frequency (0.7%) than would be expected for a mutational event; 2) they are unstable; 3) they reexpress only a subset of class II molecules; and 4) they have only been found in tetraploid cells. On the basis of previous work with 6.1.6 and the properties of reversion in 6.1.6, we propose a hypothesis for the nature of the defect in 6.1.6 and a model for the regulation of class II molecules.