title: Residual MHC class II expression on mature dendritic cells and activated B cells in RFX5-deficient mice.
abstract: Patients with major histocompatibility complex class II (MHC-II) deficiency are known to carry mutations in either the RFX complex or the trans-activator CIITA. While the pivotal role of CIITA for MHC-II gene transcription is supported by the essential absence of MHC-II molecules in CIITA-deficient mice, we demonstrate here that RFX5-/- mice retain expression of MHC-II in thymic medulla, mature dendritic cells, and activated B cells. Nevertheless, RFX5-/- mice develop a severe immunodeficiency due to the lack of MHC-II in thymic cortex, failure of positive selection of CD4+ T cells, and absence of MHC-II on resting B cells and resident or IFNgamma-activated macrophages. This differential requirement for CIITA and RFX5 in subsets of antigen-presenting cells may be specific for the mouse; it may, however, also exist in humans without having been noticed so far.
authors.affiliation: Institute for Genetics, University of Cologne, Germany.
authors.forename: B E
authors.initials: BE
authors.lastname: Clausen
authors.forename: J M
authors.initials: JM
authors.lastname: Waldburger
authors.forename: F
authors.initials: F
authors.lastname: Schwenk
authors.forename: E
authors.initials: E
authors.lastname: Barras
authors.forename: B
authors.initials: B
authors.lastname: Mach
authors.forename: K
authors.initials: K
authors.lastname: Rajewsky
authors.forename: I
authors.initials: I
authors.lastname: Förster
authors.forename: W
authors.initials: W
authors.lastname: Reith
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology*; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005802:Genes, MHC Class II; D005822:Genetic Vectors; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis; D000071701:Regulatory Factor X Transcription Factors; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; C093524:RFX5 protein, human; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D007371:Interferon-gamma