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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 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 Citation Map 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 Related Collections Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS IRF8 regulates B-cell lineage specification, commitment, and differentiation Hongsheng Wang1,*, Chang Hoon Lee1,*, Chenfeng Qi1, Prafullakumar Tailor2, Jianxun Feng1, Sadia Abbasi1, Toru Atsumi2, and Herbert C. Morse, III1 1 Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, and 2 Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 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 (HSCs). 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. Although HSCs of IRF8–/– mice failed to differentiate to B220+ B-lineage cells in vitro, the defect could be rescued by transfecting HSCs 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 HSCs 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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