The Journal of Experimental Medicine
IN Cell Analyzer 2000
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Published online 19 March 2001.
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© The Rockefeller University Press, 0022-1007/2001/3/755/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 6, March 19, 2001 755-768

Original Article

Neonatally Induced Inactivation of the Vascular Cell Adhesion Molecule 1 Gene Impairs B Cell Localization and T Cell–Dependent Humoral Immune Response

Christoph E. Leukera, Mark Labowb, Werner Müllera, and Norbert Wagnera,c

a Institute for Genetics, University of Cologne, D-50931 Cologne, Germany
b Department of Functional Genomics, Novartis Pharmaceuticals, Incorporated, Summit, New Jersey 07901
c Department of Pediatrics, University of Bonn, D-53113 Bonn, Germany
Institute for Genetics, University of Cologne, Weyertal 121, 50931 Cologne, Germany.49-221-470-518549-221-478-3196

n.wagner{at}uni-koeln.de

Vascular cellular adhesion molecule (VCAM)-1 is a membrane-bound cellular adhesion molecule that mediates adhesive interactions between hematopoietic progenitor cells and stromal cells in the bone marrow (BM) and between leukocytes and endothelial as well as dendritic cells. Since VCAM-1–deficient mice die embryonically, conditional VCAM-1 mutant mice were generated to analyze the in vivo function of this adhesion molecule. Here we show that interferon-induced Cre-loxP–mediated deletion of the VCAM-1 gene after birth efficiently ablates expression of VCAM-1 in most tissues like, for example, BM, lymphoid organs, and lung, but not in brain. Induced VCAM-1 deficiency leads to a reduction of immature B cells in the BM and to an increase of these cells in peripheral blood but not in lymphoid organs. Mature recirculating B cells are reduced in the BM. In a migration assay, the number of mature B cells that appears in the BM after intravenous injection is decreased. In addition, the humoral immune response to a T cell–dependent antigen is impaired. VCAM-1 serves an important role for B cell localization and the T cell–dependent humoral immune response.

Key Words: conditional • VCAM-1 mutant mice • B cell development • lymphocyte migration • cre/loxP • bone marrow

Abbreviations used in this paper: APC, allophycocyanin; BM, bone marrow; BrdU, bromodeoxyuridine; CXCR, CXC chemokine receptor; HPC, hematopoietic progenitor cell; HSA, heat stable antigen; ICAM, intercellular adhesion molecule; NP-CG, (4-hydroxy-3-nitrophenyl)-acetyl-chicken globulin; VCAM, vascular cell adhesion molecule; VLA, very late antigen.

© 2001 The Rockefeller University Press


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