title: Adhesion of B cell lines to endothelial cells from human lymphoid tissue modulates tyrosine phosphorylation and endothelial cell activation.
abstract: Through the production of cytokines and growth factors the endothelium of secondary lymphoid organs plays a crucial role in controlling lymphocyte migration to the lymphoid microenvironment, an essential step in the initiation of the immune response. Here we demonstrate that direct contact of B cell lines with tonsil-derived human endothelial cells resulted in changes in the phosphorylation state of endothelial cells, causing their functional activation. We found a rapid (<15-s) and transient dephosphorylation, followed by a rapid rephosphorylation of tyrosine residues of the focal adhesion kinase, paxillin, and ERK2. Maximal rephosphorylation occurred after 15-30 min of B cell contact. Preincubation of lymphoid B cells with an adhesion-blocking Ab directed against alpha(4)beta(1) integrin abrogated adhesion-mediated changes of endothelial cell tyrosine phosphorylation, suggesting that cell contact was essential. Similar patterns of tyrosine phosphorylation, but with slightly different kinetics were induced after cross-linking of beta(1) integrin or CD40 on endothelial cells. Functional activation of endothelial cells by B cell adhesion was confirmed by the production of IL-6, IL-8, monocyte chemoattractant protein-1, M-CSF, and macrophage inflammatory protein-1beta mRNA. However, direct cross-linking of beta(1) integrin and CD40 failed to accomplish the same functional activation. These data indicate that direct contact of lymphoid B cells with the endothelium from lymphoid tissue induce endothelial cell signaling, resulting in chemokine and cytokine production. This phenomenon may provide a mechanism for the remodeling of the endothelium from lymphoid tissues, thus contributing to the free migration of lymphocytes and other cells into the lymphoid organs.
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
authors.forename: Lilian I
authors.initials: LI
authors.lastname: Reyes
authors.forename: Paula
authors.initials: P
authors.lastname: Escobar
authors.forename: María R
authors.initials: MR
authors.lastname: Bono
authors.forename: Mario
authors.initials: M
authors.lastname: Rosemblatt
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System / Q000276:immunology; D051379:Mice; D014066:Palatine Tonsil / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000502:physiology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D019012:Integrin beta1; D010750:Phosphoproteins; D012333:RNA, Messenger; D014443:Tyrosine