title: Differential expression of VLA-4 integrin by resident and peripheral blood B lymphocytes. Acquisition of functionally active alpha 4 beta 1-fibronectin receptors upon B cell activation.
abstract: Very-late antigen (VLA)-4(CD49d/CD29) constitutes the only member of the beta 1 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-alpha 4 monoclonal antibodies independently of the cell activation state.
authors.affiliation: Servicio de Inmunología, Hospital de la Princesa, Univ. Autónoma de Madrid, Spain.
authors.forename: A A
authors.initials: AA
authors.lastname: Postigo
authors.forename: R
authors.initials: R
authors.lastname: Pulido
authors.forename: M R
authors.initials: MR
authors.lastname: Campanero
authors.forename: A
authors.initials: A
authors.lastname: Acevedo
authors.forename: A
authors.initials: A
authors.lastname: García-Pardo
authors.forename: A L
authors.initials: AL
authors.lastname: Corbi
authors.forename: F
authors.initials: F
authors.lastname: Sanchez-Madrid
authors.forename: M O
authors.initials: MO
authors.lastname: De Landazuri
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D002448:Cell Adhesion; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D008213:Lymphocyte Activation; D014066:Palatine Tonsil / Q000166:cytology / Q000378:metabolism; D010581:Peyer's Patches / Q000166:cytology / Q000378:metabolism; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000378:metabolism*; D016029:Receptors, Very Late Antigen / Q000378:metabolism*; D013997:Time Factors
chemical_list: D005353:Fibronectins; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D016029:Receptors, Very Late Antigen