Novel mutations within the RFX-B gene and partial rescue of MHC and related genes through exogenous class II transactivator in RFX-B-deficient cells

MWC class II deficiency or bare lymphocyte syndrome is a severe combined im munodeficiency caused by defects in MHC-specific regulatory factors. Fibrob lasts derived from two recently identified bare lymphocyte syndrome patient s, EBA and FZA, were found to contain novel mutations in the RFX-B gene, RF X-B encodes a component of the RFX transcription factor that functions in t he assembly of multiple transcription factors on MHC class II promoters. Un like RFX5- and RFXAP-deficient cells, transfection of exogenous class II tr ansactivator (CIITA) into these RFX-B deficient fibroblasts resulted in the induction of HLA-DR and HLA-DP and, to a lesser extent, HLA-DQ. Similarly, CIITA-mediated induction of MHC class I, beta(2),-microglobulin, and invar iant chain genes was also found in these RFX-B-deficient fibroblasts, Expre ssion of wild-type RFX-B completely reverted the noted deficiencies in thes e cells. Transfection of CIITA into Ramia cells, a B cell line that does no t produce a stable RFX-B mRNA, resulted in induction of an MHC class II rep orter, suggesting that CIITA overexpression may partially override the RFX- B defect.