Meissner Anja, Zilles Olaf, Varona Rosa, Jozefowski Katrin, Ritter Uwe, Marquez Gabriel, Hallmann Rupert, Korner Heinrich
Interdisciplinary Center for Clinical Research, Departmen of Experimental Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany.
Blood. 2003 Oct 15;102(8):2724-7. doi: 10.1182/blood-2003-01-0007. Epub 2003 Jun 19.
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 protein-mediated 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.
