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Differential expression of VLA‐4 integrin by resident and peripheral blood B lymphocytes. Acquisition of functionally active α4β1‐fibronectin receptors upon B cell activation

Abstract:

Very‐late antigen (VLA)‐4 (CD49d/CD29) constitutes the only member of the β1 integrin family that plays a role in the interaction of lymphoid cells with both extracellular matrix and endothelial cells through two identified ligands: fibronectin (FN) and VCAM‐1, respectively. The expression and functional activity of VLA‐4 has been studied in different maturation and activation stages of B cells from several cellular compartments. Resident B lymphocytes of different lymphoid organs were almost negative for VLA‐4 as detected by both immunoperoxidase staining and flow cytometry analysis. However, a high expression of both chains of this heterodimer was observed when tonsillar B cells were activated in vitro with different stimuli, such as phorbol esters or Staphylococcus aureus Cowan I (SAC). Both nonactivated and in vitro activated B cells from peripheral blood constitutively expressed high levels of this surface antigen. The induced expression of VLA‐4 after activation of tonsillar B lymphocytes was accompanied by the acquisition of the capacity to bind to a 38‐kDa proteolytic fragment, containing the connecting segment I domain, of FN. Interestingly, nonactivated peripheral blood B cells were unable to attach to this FN fragment, in spite of their constitutive expression of VLA‐4, and only acquired this functional capacity after cell activation with phorbol esters and SAC. This FN‐binding acquisition was not affected by preincubation with inhibitors of protein and RNA synthesis. These results underline that the FN‐binding activity of VLA‐4 is dependent on processes affecting cellular activation as described for other members of the integrin family. By contrast, VLA‐4‐mediated homotypic aggregation of peripheral blood B cells could be triggered by anti‐α4 monoclonal antibodies independently of the cell activation state. Copyright © 1991 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim