Vascular cell adhesion molecule-1 and the integrin VLA-4 mediate adhesion of human B cell precursors to cultured bone marrow adherent cells.

Abstract

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 VLA4 and VLA-5 were the only adhesion proteins expressed at higher levels in B cell precursors than mature B cells.Antibodies to the a and ft chains of VLA4, 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 VLA4, anti-fibronectin antibody and a soluble fibronectin fragment containing the VLA4 binding domain did not block adhesion, suggesting that VLA4 is involved in adhesion of B cell precursors, but not as a fibronectin receptor. Vascular cell adhesion molecule-l (VCAM-1), the other known counterreceptor for VLA4, was identified on bone marrowderived fibroblasts, and anti-VCAM-1 significantly blocked adhesion of normal B cell precursors to bone marrow-derived fibroblasts, indicating that VLA4/VCAM-1 interactions are important in adhesion of B cell precursors to the bone marrow microenvironment. (J. Clin. Invest. 1991. 88:995-1004

CXCR4 chemokine receptors (CD184) and α4β1 integrins mediate spontaneous migration of human CD34+ progenitors and acute myeloid leukaemia cells beneath marrow stromal cells (pseudoemperipolesis)

“…Pseudoemperipolesis has been described earlier for B-and T-lineage cell migration beneath marrow stroma or synovial fibroblasts (Hiai et al, 1981;Hewson et al, 1996;Takeuchi et al, 1999;Bradstock et al, 2000), and has been demonstrated to involve a4b1 and a5b1 (VLA-4, VLA-5 or CD49d, CD49e) integrin binding to corresponding stromal ligands (fibronectin and VCAM-1) (Miyake et al, 1992). The importance of a4b1 and a5b1 integrins in heterotypic adherence between precursor cell lines (pre-B Nalm-6 and multipotential UT-7) and marrow stromal cells has been demonstrated by several investigators (Ryan et al, 1991;Patrick et al, 1995;Robledo et al, 1998;Turner et al, 1998), but the molecular mechanism of haematopoietic stem cell migration beneath stromal cells has not yet been defined. It has been noted, however, that integrins alone mediate only the initial attachment of precursor or AML cells to stroma, but are not sufficient for the retention or subsequent migration beneath the stromal cells (Miyake et al, 1992;Bendall et al, 1993;Patrick et al, 1995).…”

Difference between Expression of Adhesion Molecules on CD34 + Cells from Bone Marrow and G‐CSF‐Stimulated Peripheral Blood

“…CD58 (LFA-3) is the ligand for CD2 and might be involved in interaction between T cells and HPC [11]. Several adhesion molecules have been found to be expressed on CD34 + cells: CD44, CD53, CD56, CD31, VLA-4 (CD29/CD49d), VLA-5 (CD29/CD49e), LFA-1 (CD18/CD11a) and Mac-1 (CD18/CD11b) [9,[12][13][14][15][16][17][18][19][20][21][22].…”

Peripheral accumulation of newly produced T and B lymphocytes in natalizumab-treated multiple sclerosis patients

“…It is likely, therefore, that the drug can also affect T-and B-cell output from their production sites. Furthermore, the different expression of VLA-4 on lymphocyte subpopulations, with its basal levels higher on B than on T cells, on CD8 + than on CD4 + T cells, and on memory than on naïve cells [10,11] could also imply that natalizumab treatment can differentially influence the homeostasis of lymphocyte subsets. To verify these possibilities, we monitored the changes in the number of T and B lymphocytes recently released from thymus and BM in patients treated with natalizumab by quantifying the number of T-cell receptor (TCR) excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) [12,13].…”