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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1776-1784. Prepublished online as a Blood First Edition Paper on November 22, 2005; DOI 10.1182/blood-2005-08-3470. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-08-3470v1 107/5/1776    most recent Alert me when this article is cited Alert me if a correction is posted 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 Lai, L. Articles by Goldschneider, I. Search for Related Content PubMed PubMed Citation Articles by Lai, L. Articles by Goldschneider, I. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 26, 2005 Accepted October 25, 2005 A recombinant single-chain IL-7/HGF hybrid cytokine induces juxtacrine interactions of the IL-7 and HGF (c-met) receptors and stimulates the proliferation of CFU-S12, common lymphoid progenitors (CLP) and pre-pro-B cells Laijun Lai, Richard A Zeff, and Irving Goldschneider* Department of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT, USA * Corresponding author; email: goldsch{at}neuron.uchc.edu. A novel recombinant IL-7/hepatocyte growth factor chain (IL-7/HGF) hybrid cytokine was constructed as a single-chain (sc) composed of IL-7 and HGF connected by a flexible linker. Unlike rIL-7, which stimulated pro-B cells and pre-B cells only, scIL-7/HGF stimulated the proliferation of pre-pro-B cells, CLPs and CFU-S12 in cultures of IL-7-/- mouse BM cells. When injected in vivo, 3 to 4-fold more splenic B-lineage cells appeared in recipients of BM cells from the scIL-7/HGF-stimulated cultures than from rIL-7-stimulated cultures. Moreover, on a per cell basis, scIL-7/HGF culture-generated cells produced 16 to 20-fold more BM and splenic B-lineage cells than did normal BM cells. Antibody blocking, receptor phosphorylation and confocal microscopy demonstrated that scIL-7/HGF signals though both the IL-7 and HGF (c-Met) receptors, which form IL-7R/c-Met complexes on the surface of CLPs and pre-pro-B cells. In addition, the IL-7R chain, c chain and c-met were coisolated from purified CLP and pre-pro-B cells on scIL-7/HGF affinity gels, indicating that they are major components of the IL-7/HGF receptor. Hence, the present results demonstrate that the IL-7/HGF hybrid cytokine efficiently and selectively stimulates the most primitive B-lineage precursors in BM by inducing juxtacrine interactions between the IL-7 and c-Met receptors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A fine romance: IL-7 and HGF Crystal L. Mackall Blood 2006 107: 1739-1740. [Full Text] [PDF] This article has been cited by other articles: S. L. Kalis, S.-K. Zhai, P.-C. Yam, P. L. Witte, and K. L. Knight Suppression of B lymphopoiesis at a lymphoid progenitor stage in adult rabbits Int. Immunol., June 1, 2007; 19(6): 801 - 811. [Abstract] [Full Text] [PDF]

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