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Blood, 1 August 2008, Vol. 112, No. 3, pp. 551-559. Prepublished online as a Blood First Edition Paper on May 27, 2008; DOI 10.1182/blood-2007-11-125930. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2007-11-125930v1 112/3/551    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 Guo, F. Articles by Weih, F. Search for Related Content PubMed PubMed Citation Articles by Guo, F. Articles by Weih, F. Related Collections Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Lack of nuclear factor-B2/p100 causes a RelB-dependent block in early B lymphopoiesis Feng Guo1, Simone Tänzer1, Meinrad Busslinger2, and Falk Weih1,3 1 Research Group Immunology, Leibniz-Institute for Age Research—Fritz-Lipmann-Institute, Jena, Germany; 2 Research Institute of Molecular Pathology, Vienna, Austria; and 3 Friedrich-Schiller-University, Jena, Germany Nuclear factor-B (NF-B) transcription factors regulate B-cell development and survival. However, whether they also have a role during early steps of B-cell differentiation is largely unclear. Here, we show that constitutive activation of the alternative NF-B pathway in p100–/– knockin mice resulted in a block of early B-cell development at the transition from the pre–pro-B to the pro–B-cell stage due to enhanced RelB activity. Expression of the essential B-cell transcription factors EBF and in particular Pax5 was reduced in p100–/– B-cell precursors in a RelB-dependent manner, resulting in reduced mRNA levels of B lineage-specific genes. Moreover, enhanced RelB function in p100–/– B-cell precursors was accompanied by increased expression of B lineage–inappropriate genes, such as C/EBP, correlating with a markedly increased myeloid differentiation potential of p100–/– progenitor B cells. Ectopic expression of Pax5 in hematopoietic progenitors restored early B-cell development in p100–/– bone marrow, suggesting that impaired early B lymphopoiesis in mice lacking the p100 inhibitor may be due to down-regulation of Pax5 expression. Thus, tightly controlled p100 processing and RelB activation is essential for normal B lymphopoiesis and lymphoid/myeloid lineage decision in bone marrow. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Wu, M. Yamamoto, S. Akira, and S.-C. Sun Regulation of hematopoiesis by the K63-specific ubiquitin-conjugating enzyme Ubc13 PNAS, December 8, 2009; 106(49): 20836 - 20841. [Abstract] [Full Text] [PDF] T. Matsumura, J. Kawamura-Tsuzuku, T. Yamamoto, K. Semba, and J.-i. Inoue TRAF-Interacting Protein with a Forkhead-Associated Domain B (TIFAB) Is a Negative Regulator of the TRAF6-Induced Cellular Functions J. Biochem., September 1, 2009; 146(3): 375 - 381. [Abstract] [Full Text] [PDF]

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