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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1396-1403. Prepublished online as a Blood First Edition Paper on October 30, 2007; DOI 10.1182/blood-2007-08-110106. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-08-110106v1 111/3/1396    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 Ma, S. Articles by Lu, R. Search for Related Content PubMed PubMed Citation Articles by Ma, S. Articles by Lu, R. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Interferon regulatory factors 4 and 8 induce the expression of Ikaros and Aiolos to down-regulate pre–B-cell receptor and promote cell-cycle withdrawal in pre–B-cell development Shibin Ma1, Simanta Pathak1, Long Trinh1, and Runqing Lu1 1 Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha Pre-B lymphocytes consist of 2 distinct cell populations: large pre-B and small pre-B. The large pre-B cells are newly generated pre-B cells that express pre–B-cell receptor (pre-BCR) on the surface and are highly proliferative; small pre-B cells are derived from large pre-B cells that have down-regulated pre-BCR and withdrawn from cell cycle. The molecular events that mediate the transition from cycling pre-B to small, resting pre-B have not been fully elucidated. Here, we show that interferon regulatory factors 4 and 8 (IRF4,8) suppress surrogate light chain expression and down-regulate pre-BCR in pre-B cells. Our studies further reveal that IRF4,8 induce the expression of Ikaros and Aiolos in pre-B cells, and reconstitution of expression of either one is sufficient to suppress surrogate light chain expression and down-regulate pre-BCR in pre-B cells lacking IRF4,8. Interestingly, our results also indicate that pre-B cells undergo growth inhibition and cell-cycle arrest in the presence of IRF4,8. Moreover, we provide evidence that Ikaros and Aiolos are indispensable for the down-regulation of pre-BCR and the cell-cycle withdrawal mediated by IRF4,8. Thus, IRF4,8 orchestrate the transition from large pre-B to small pre-B cells by inducing the expression of Ikaros and Aiolos. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Pathak, S. Ma, L. Trinh, and R. Lu A Role for Interferon Regulatory Factor 4 in Receptor Editing Mol. Cell. Biol., April 15, 2008; 28(8): 2815 - 2824. [Abstract] [Full Text] [PDF]

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