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The Journal of Immunology, 2002, 169: 5881-5888.
Copyright © 2002 by The American Association of Immunologists

Adhesion of B Cell Lines to Endothelial Cells from Human Lymphoid Tissue Modulates Tyrosine Phosphorylation and Endothelial Cell Activation1

Lilian I. Reyes*, Paula Escobar*, María R. Bono* and Mario Rosemblatt2,*,{dagger}

* Departamento de Biología, Facultad de Ciencias, Universidad de Chile and Millennium Institute for Fundamental and Applied Biology; and {dagger} Fundación Ciencia para la Vida, Santiago, Chile

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-1{beta} 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.




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