Vascular cell adhesion molecule-1 and the integrin VLA-4 mediate adhesion of human B cell precursors to cultured bone marrow adherent cells.
Adhesion of B cell precursors to accessory cells in the bone marrow microenvironment may be required for normal early B cell development. Human bone marrow B cell precursors adhere more avidly than mature B cells to bone marrow-derived fibroblasts. To determine the mechanism of this adhesion, expression of adhesion proteins on human B precursor cells and cell lines was measured by flow cytometry. The very late antigen (VLA) integrins VLA-4 and VLA-5 were the only adhesion proteins expressed at higher levels in B cell precursors than mature B cells. Antibodies to the alpha and beta chains of VLA-4, but not VLA-5, significantly blocked binding to bone marrow-derived fibroblasts of immature B cells and cell lines. Although fibronectin is a ligand for VLA-4, anti-fibronectin antibody and a soluble fibronectin fragment containing the VLA-4 binding domain did not block adhesion, suggesting that VLA-4 is involved in adhesion of B cell precursors, but not as a fibronectin receptor. Vascular cell adhesion molecule-1 (VCAM-1), the other known counterreceptor for VLA-4, was identified on bone marrow-derived fibroblasts, and anti-VCAM-1 significantly blocked adhesion of normal B cell precursors to bone marrow-derived fibroblasts, indicating that VLA-4/VCAM-1 interactions are important in adhesion of B cell precursors to the bone marrow microenvironment.
Ryan
D H
DH
Department of Pathology, University of Rochester Medical Center, New York 14642.
Nuccie
B L
BL
Abboud
C N
CN
Winslow
J M
JM
D000328:Adult; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology*; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016029:Receptors, Very Late Antigen / Q000032:analysis / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D013755:Tetradecanoylphorbol Acetate