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The Journal of Immunology, 2008, 181, 383-392
Copyright © 2008 by The American Association of Immunologists, Inc.

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IL-7 Specifies B Cell Fate at the Common Lymphoid Progenitor to Pre-ProB Transition Stage by Maintaining Early B Cell Factor Expression1

Kazu Kikuchi, Hirotake Kasai, Akiko Watanabe, Anne Y. Lai and Motonari Kondo2

Department of Immunology, Duke University Medical Center, Durham, NC 27710

IL-7 plays a critical role in B cell fate decision by regulating early B cell factor (EBF) expression. However, it was not clear when IL-7 stimulation is necessary in hemato-/lymphopoiesis in adult mice. Here we show that pre-proB cells derived from IL-7–/– mice have lost B cell potential, despite up-regulation of EBF expression following IL-7 stimulation. Pre-proB cells from wild-type mice can give rise to proB cells in the absence of IL-7. In this case, EBF up-regulation during the transition from the pre-proB to proB stages occurs normally. In contrast, EBF expression by IL-7–/– pre-proB cells after IL-7 stimulation is ~20 times lower than wild-type pre-proB cells. In addition, only multipotent progenitors with higher levels of ectopic EBF can give rise to proB cells in the absence of IL-7. Therefore, the primary function of IL-7 before the pre-proB stage in B cell development is to maintain the EBF expression level above a certain threshold, which is necessary for pre-proB cells to further transit to the proB stage.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by the Duke Stem Cell Research Program Annual Award and National Institutes of Health Grants AI056123 and CA098129 (to M.K.) and National Institutes of Health Grant AI52077 to A.Y.L. M.K. is a scholar of the Leukemia and Lymphoma Society.

2 Address correspondence and reprint requests to Dr. Motonari Kondo, 101 Jones Building, Duke University Medical Center 3010, Research Drive, Durham, NC 27710. E-mail address: motonari.kondo{at}duke.edu

3 Abbreviations used in this paper: {gamma}c, cytokine receptor common {gamma}-chain; EBF, early B cell factor; CLP, common lymphoid progenitor; WT, wild type; HSC, hemopoietic stem cell; ER, estrogen receptor; 4-HT, 4-hydroxytamoxifen; PI, propidium iodide; SCF, stem cell factor; DC, dendritic cell; MPP, multipotent progenitor; Flt3L, Flt3 ligand; CIS, cytokine-inducible SH2 protein.




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Y. K. Parrish, I. Baez, T.-A. Milford, A. Benitez, N. Galloway, J. W. Rogerio, E. Sahakian, M. Kagoda, G. Huang, Q.-L. Hao, et al.
IL-7 Dependence in Human B Lymphopoiesis Increases during Progression of Ontogeny from Cord Blood to Bone Marrow
J. Immunol., April 1, 2009; 182(7): 4255 - 4266.
[Abstract] [Full Text] [PDF]




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