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Subpopulations of bone marrow fibroblasts support VLA-4-mediated migration of B-cell precursors

J Tang, G Scott and DH Ryan

Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, NY.

Proliferation of normal human lymphoid progenitors in culture is dependent on interaction with bone marrow-derived fibroblast-like cells (BM-FB). To investigate possible heterogeneity in this lymphoid- supportive microenvironment, we studied the interaction of a human B- precursor cell line (NALM-6) with BM-FB. NALM-6 cells associate with BM- FB by either adhesion or migration underneath the fibroblast. Individual fibroblasts in the BM-FB layer showed significant variation in the number of migrating NALM-6 cells. Migration of NALM-6 cells was primarily VLA-4-dependent, although residual migration observable after blocking with anti-VLA-alpha 4 antibody was inhibited by anti-VLA-alpha 5 antibody. Migration was not inhibited by blocking either of the known VLA-4 counterreceptors (VCAM-1 or fibronectin), although slight inhibition was observed using a combination of blocking antibodies to VCAM-1 and fibronectin. In contrast, NALM-6 adhesion without migration was significantly inhibitable by anti-VCAM-1 antibody. VCAM-1 or fibronectin expression on individual BM-FB did not correlate with NALM- 6 migration. These results indicate that the adhesion and migration of human B-lymphoid precursors in the bone marrow microenvironment are mechanistically separable events and suggest the possibility of novel VLA-4 ligand(s), which may be important in human lymphopoiesis. Subpopulations of cells in the bone marrow microenvironment may preferentially support important aspects of lymphoid progenitor development.

Volume 82, Issue 11, pp. 3415-3423, 12/01/1993
Copyright © 1993 by The American Society of Hematology


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  Copyright © 1993 by American Society of Hematology         Online ISSN: 1528-0020