Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 193, Issue 6, Pages 755-767Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.193.6.755
Keywords
conditional VCAM-1 mutant mice; B cell development; lymphocyte migration; cre/loxP; bone marrow
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Vascular cellular adhesion molecule (VCAM)-1 is a membrane-bound cellular adhesion molecule that mediates adhesive interactions between hematopoietic progenitor cells and stromal cells ill 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 trample, BM, lymphoid organs, and lung, but not ill 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 die T cell-dependent humoral immune response.
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