title: IRF8 governs expression of genes involved in innate and adaptive immunity in human and mouse germinal center B cells.
abstract: IRF8 (Interferon Regulatory Factor 8) is a transcription factor expressed throughout B cell differentiation except for mature plasma cells. Previous studies showed it is part of the transcriptional network governing B cell specification and commitment in the bone marrow, regulates the distribution of mature B cells into the splenic follicular and marginal zone compartments, and is expressed at highest levels in germinal center (GC) B cells. Here, we investigated the transcriptional programs and signaling pathways affected by IRF8 in human and mouse GC B cells as defined by ChIP-chip analyses and transcriptional profiling. We show that IRF8 binds a large number of genes by targeting two distinct motifs, half of which are also targeted by PU.1. Over 70% of the binding sites localized to proximal and distal promoter regions with ∼25% being intragenic. There was significant enrichment among targeted genes for those involved in innate and adaptive immunity with over 30% previously defined as interferon stimulated genes. We also showed that IRF8 target genes contributes to multiple aspects of the biology of mature B cells including critical components of the molecular crosstalk among GC B cells, T follicular helper cells, and follicular dendritic cells.
authors.affiliation: Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Dong-Mi
authors.initials: DM
authors.lastname: Shin
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D050835:Interferon Regulatory Factors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099185:Interferon Regulatory Factor-8; D000099232:Proto-Oncogene Protein Spi-1
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