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* Departamento de Biología, Facultad de Ciencias, Universidad de Chile and Millennium Institute for Fundamental and Applied Biology; and
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
1530 min of B cell contact. Preincubation of lymphoid B cells with an
adhesion-blocking Ab directed against
4
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
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
mRNA. However, direct cross-linking of
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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