The Journal of Experimental Medicine
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Published 2 September 2002. doi:10.1084/jem.20020784
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© Rockefeller University Press, 0022-1007/2002/9/705/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 5, September 2, 2002 705-711

Brief Definitive Report

 The Earliest Step in B Lineage Differentiation from Common Lymphoid Progenitors Is Critically Dependent upon Interleukin 7

Juli P. Miller1, David Izon1, William DeMuth2, Rachel Gerstein3, Avinash Bhandoola1 and David Allman1,2

1 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
2 Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
3 Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655

Address correspondence to David Allman, University of Pennsylvania School of Medicine, Biomedical Research Building 2,3, 421 Curie Blvd., Room 553, Philadelphia, PA 19104. Phone: 215-746-5547; Fax: 215-573-8590. E-mail: dallman{at}mail.med.upenn.edu

Little is known about the signals that promote early B lineage differentiation from common lymphoid progenitors (CLPs). Using a stromal-free culture system, we show that interleukin (IL)-7 is sufficient to promote the in vitro differentiation of CLPs into B220+ CD19+ B lineage progenitors. Consistent with current models of early B cell development, surface expression of B220 was initiated before CD19 and was accompanied by the loss of T lineage potential. To address whether IL-7 receptor (R) activity is essential for early B lineage development in vivo, we examined the frequencies of CLPs and downstream pre–pro- and pro-B cells in adult mice lacking either the {alpha} chain or the common gamma chain ({gamma}c) of the IL-7R. The data indicate that although {gamma}c-/- mice have normal frequencies of CLPs, both {gamma}c-/- and IL-7R{alpha}-/- mice lack detectable numbers of all downstream early B lineage precursors, including pre–pro-B cells. These findings challenge previous notions regarding the point in B cell development affected by the loss of IL-7R signaling and suggest that IL-7 plays a key and requisite role during the earliest phases of B cell development.

Key Words: B lymphocytes • hematopoiesis • cellular differentiation • cytokine • development


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