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Blood, 15 October 2003, Vol. 102, No. 8, pp. 2724-2727. Prepublished online as a Blood First Edition Paper on June 19, 2003; DOI 10.1182/blood-2003-01-0007.
CHEMOKINES CC chemokine ligand 20 partially controls adhesion of naive B cells to activated endothelial cells under shear stressFrom the Interdisciplinary Center for Clinical Research, the Department for Experimental Medicine I of the University Erlangen-Nürnberg, Nikolaus-Fiebiger-Center for Molecular Medicine, Erlangen, Germany; the Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología, Universidad Autónoma, Madrid, Spain; and the Department of Experimental Pathology, Lund University, Sweden.
Chemokines are thought to control lymphocyte recruitment to the inflamed endothelium. To dissect chemokine-mediated adhesion, binding of ex vivo isolated splenocytes to tumor necrosis factor (TNF)activated endothelial cells was analyzed under shear stress. We observed specific adhesion of naive follicular B cells, which could be blocked by pertussis toxin. This indicated a G proteinmediated binding and pointed at a contribution of chemokine receptors to B-cell adhesion. Analysis of chemokines expressed by TNF-activated endothelial cells showed that CC chemokine ligand 2 (CCL2), CCL17, and CCL20 were up-regulated. Only on follicular B cells was the cognate receptor for CCL20, CC chemokine receptor 6 (CCR6), expressed strongly, and a functional transmigration assay with CCR6-negative B cells demonstrated conclusively the sole signaling of CCL20 through CCR6. Desensitization of CCR6 on naive B cells with CCL20 resulted in receptor down-regulation and reduced B-cell adhesion. We conclude that CCL20 plays a vital role in B-cell adhesion to the inflamed endothelium.
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