Congenital immunodeficiencies associated with absence of HLA class II antigens on lymphocytes result from distinct mutations in trans-acting factors.

Coordinate regulation of HLA class II gene expression during development and coinduction of class II genes by soluble factors suggests that common trans-acting factor(s) control expression of these genes. In B-lymphoblastoid cell lines derived from two independent class II-deficient bare lymphocyte syndrome patients, we observed a drastic decrease in transcription rates of the class II genes. When these cell lines are fused, class II genes are reexpressed, indicating that immunodeficiencies in bare lymphocyte syndrome patients are the result of two distinct mutations. Further studies show that genes governing the expression of class II antigens fall into at least three complementation groups; two of these were previously unidentified in mutant cell lines generated in vitro. In addition, we report the identification of two discrete complexes, NFX1.1 and NFX1.2, that bind to the DRA X consensus element. Though the mutation in at least one mutant line generated in vitro (RJ2.2.5) affects products functioning via interaction with the X box, clear alterations in either NFX1.1 or NFX1.2 are not found in any of the mutant cell lines.