title: IFN regulatory factor 8 restricts the size of the marginal zone and follicular B cell pools.
abstract: Transcriptional control of marginal zone (MZ) and follicular (FO) B cell development remains incompletely understood. The transcription factor, IFN regulatory factor (IRF)8, is known to play important roles in the differentiation of early B cells. In this article, we demonstrate that IRF8 is also required for normal development of MZ and FO B cells. Mice with a conventional knockout of Irf8 (IRF8(-/-)) or a point mutation in the IRF association domain of IRF8 had increased numbers of MZ B cells. To determine the B cell-intrinsic effects of IRF8 deficiency, we generated mice with a conditional allele of Irf8 crossed with CD19-Cre mice (designated IRF8-conditional knockout [CKO]). These mice had enlarged MZ and increased numbers of MZ and FO B cells compared with controls. The FO B cells of CKO mice exhibited reduced expression of CD23 and moderately increased expression of CD21. Gene-expression profiling showed that increased B cell production in IRF8-CKO mice was associated with changes in expression of genes involved in regulation of transcription, signaling, and inflammation. Functional studies showed that IRF8-CKO mice generated normal Ab responses to T-independent and T-dependent Ags. Thus, IRF8 controls the expansion and maturation of MZ and FO B cells but has little effect on B cell function.
authors.affiliation: Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Feng
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Wang
authors.forename: Dong-Mi
authors.initials: DM
authors.lastname: Shin
authors.forename: Marek
authors.initials: M
authors.lastname: Masiuk
authors.forename: Chen-Feng
authors.initials: CF
authors.lastname: Qi
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D050835:Interferon Regulatory Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D017354:Point Mutation; D017434:Protein Structure, Tertiary / Q000235:genetics; D013154:Spleen / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D000099185:Interferon Regulatory Factor-8
chemical_list: D050835:Interferon Regulatory Factors; D000099185:Interferon Regulatory Factor-8