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Publication : IRF8 governs expression of genes involved in innate and adaptive immunity in human and mouse germinal center B cells.

First Author  Shin DM Year  2011
Journal  PLoS One Volume  6
Issue  11 Pages  e27384
PubMed ID  22096565 Mgi Jnum  J:180972
Mgi Id  MGI:5308489 Doi  10.1371/journal.pone.0027384
Citation  Shin DM, et al. (2011) IRF8 governs expression of genes involved in innate and adaptive immunity in human and mouse germinal center B cells. PLoS One 6(11):e27384
abstractText  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 approximately 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.
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