Neonatally induced inactivation of the vascular cell adhesion molecule 1 gene impairs B cell localization and T cell-dependent humoral immune response.
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.
Institute for Genetics, University of Cologne, Weyertal 121, D-50931 Cologne, Germany.
C E
CE
Leuker
M
M
Labow
W
W
Müller
N
N
Wagner
D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D018390:Gene Targeting / Q000379:methods; D007072:Immunoglobulin D / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*
D007072:Immunoglobulin D; D007075:Immunoglobulin M; D019010:Vascular Cell Adhesion Molecule-1