title: 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.
abstract: MHC class II deficiency or bare lymphocyte syndrome is a severe combined immunodeficiency caused by defects in MHC-specific regulatory factors. Fibroblasts derived from two recently identified bare lymphocyte syndrome patients, EBA and FZA, were found to contain novel mutations in the RFX-B gene. RFX-B encodes a component of the RFX transcription factor that functions in the assembly of multiple transcription factors on MHC class II promoters. Unlike RFX5- and RFXAP-deficient cells, transfection of exogenous class II transactivator (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, beta2-microglobulin, and invariant chain genes was also found in these RFX-B-deficient fibroblasts. Expression of wild-type RFX-B completely reverted the noted deficiencies in these cells. Transfection of CIITA into Ramia cells, a B cell line that does not produce a stable RFX-B mRNA, resulted in induction of an MHC class II reporter, suggesting that CIITA overexpression may partially override the RFX-B defect.
authors.affiliation: Department of Microbiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: U M
authors.initials: UM
authors.lastname: Nagarajan
authors.forename: A
authors.initials: A
authors.lastname: Peijnenburg
authors.forename: S J
authors.initials: SJ
authors.lastname: Gobin
authors.forename: J M
authors.initials: JM
authors.lastname: Boss
authors.forename: P J
authors.initials: PJ
authors.lastname: van den elsen
mesh_terms: D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015152:Blotting, Northern; D002460:Cell Line; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D005802:Genes, MHC Class II / Q000276:immunology*; D005816:Genetic Complementation Test; D005822:Genetic Vectors / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000276:immunology*; D009687:Nuclear Proteins; D012313:RNA / Q000032:analysis; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000494:pharmacology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects / Q000276:immunology; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; C117892:RFXANK protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D012313:RNA