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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4028-4038. Prepublished online as a Blood First Edition Paper on September 17, 2008; DOI 10.1182/blood-2008-01-129049. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-01-129049v1 112/10/4028    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wang, H. Articles by Morse, H. C Search for Related Content PubMed PubMed Citation Articles by Wang, H. Articles by Morse, H. C, III Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 10, 2008 Accepted August 19, 2008 IRF8 regulates B cell lineage specification, commitment and differentiation Hongsheng Wang*, Chang Hoon Lee, Chenfeng Qi, Prafullakumar Tailor, Jianxun Feng, Sadia Abbasi, Toru Atsumi, and Herbert C Morse III Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, Rockville, MD, United States Laboraotry of Molecular Growth Regulation, National Institute of Child Health and Human Development, Bethesda, MD, United States * Corresponding author; email: wanghongs{at}niaid.nih.gov. PU.1, IKAROS, E2A, EBF and PAX5 comprise a transcriptional network that orchestrates B cell lineage specification, commitment and differentiation. Here we identify interferon regulatory factor 8 (IRF8) as another component of this complex, and show that it also modulates lineage choice by hematopoietic stem cells (HSC). IRF8 binds directly to an IRF8/Ets consensus sequence located in promoter regions of Sfpi1 and Ebf1, which encode PU.1 and EBF, respectively and is associated with transcriptional repression of Sfpi1 and transcriptional activation of Ebf1. Bone marrows of IRF8 knockout mice (IRF8-/-) had significantly reduced numbers of pre-pro-B cells and increased numbers of myeloid cells. While HSC of IRF8-/- mice failed to differentiate to B220+ B lineage cells in vitro, the defect could be rescued by transfecting HSC with wild type but not with a signaling-deficient IRF8 mutant. In contrast, overexpression of IRF8 in HSC-differentiated progenitor cells resulted in growth inhibition and apoptosis. We also found that IRF8 was expressed at higher levels in pre-pro-B cells than more mature B cells in wild type mice. Together, these results indicate that IRF8 modulates lineage choice by HSC and is part of the transcriptional network governing B cell lineage specification, commitment and differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. X. Zhou, C. H. Lee, C. F. Qi, H. Wang, Z. Naghashfar, S. Abbasi, and H. C. Morse III IFN Regulatory Factor 8 Regulates MDM2 in Germinal Center B Cells J. Immunol., September 1, 2009; 183(5): 3188 - 3194. [Abstract] [Full Text] [PDF]

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