Regulation of human B-cell precursor adhesion to bone marrow stromal cells by cytokines that exert opposing effects on the expression of vascular cell adhesion molecule-1 (VCAM-1)

Blood. 1993 May 1;81(9):2272-82.


Self-renewal and differentiation of B-cell precursors is dependent on interactions with bone marrow (BM) stromal cells and associated extracellular matrix. We have recently developed an interleukin (IL)-7-dependent, BM-derived stromal cell culture that supports the growth of normal human B-cell precursors. In the current study, we have characterized the constitutive expression, cytokine-regulated expression, and function of adhesion molecules on BM stromal cells that are critical for adhesion of B-cell precursors. Flow cytometric analysis showed that cultured adult BM stromal cells expressed higher constitutive levels of vascular cell adhesion molecule (VCAM)-1 than intercellular adhesion molecule (ICAM)-1 (CD54). IL-1 beta upregulated VCAM-1 and CD54 in a dose-dependent manner, whereas IL-4 upregulated VCAM-1, but had no effect on CD54. In contrast, transforming growth factor (TGF)-beta decreased the level of BM stromal cell VCAM-1. Using an assay to measure the adhesion of 51Cr-labeled B-cell precursors to BM stromal cells, we observed a direct correlation between cytokine-regulated levels of VCAM-1 and the capacity of stromal cells to support the adhesion of B-cell precursors. Blocking studies using a panel of monoclonal antibodies (MoAb) showed that adhesion of B-cell precursors to untreated and cytokine-treated (IL-1 beta, IL-4) BM stromal cells was mediated by very late antigen (VLA)-4 (CD49d/CD29) and VCAM-1. Adhesion of B-cell precursors could also be enhanced by direct stimulation with MoAb to the CD29 subunit. Our collective results indicate that B-cell precursor/BM stromal cell adhesion is mediated by a VLA-4-VCAM-1 interaction, which in turn can be regulated at the level of the BM stromal cell by cytokines that specifically increase or decrease cell surface VCAM-1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antigens, CD / analysis
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / physiology*
  • Bone Marrow / drug effects
  • Bone Marrow / physiology*
  • Bone Marrow Cells
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / metabolism*
  • Cytokines / pharmacology*
  • Fetus
  • Fibroblast Growth Factor 2 / pharmacology
  • Flow Cytometry
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukins / pharmacology*
  • Kinetics
  • Lipopolysaccharides / pharmacology
  • Recombinant Proteins / pharmacology
  • Transforming Growth Factor beta / pharmacology
  • Vascular Cell Adhesion Molecule-1


  • Antigens, CD
  • Cell Adhesion Molecules
  • Cytokines
  • Interleukins
  • Lipopolysaccharides
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Vascular Cell Adhesion Molecule-1
  • Fibroblast Growth Factor 2
  • Interferon-gamma