THE CHEMOKINE SDF-1-ALPHA TRIGGERS A CHEMOTACTIC RESPONSE AND INDUCESCELL POLARIZATION IN HUMAN B-LYMPHOCYTES

We studied the expression and possible functional role of chemokine re ceptors CXCR3, CXCR4 and CCR5 in normal human B lymphocytes. B cells f rom both peripheral blood and tonsils expressed high levels of CXCR4 b ut not the other chemokine receptors tested. CXCR4 ligand, stromal cel l-derived factor (SDF)-1 alpha, elicited a potent chemotactic response and induced a polarized motile phenotype in B cells, resulting in red istribution of the adhesion molecule ICAM-3 to a posterior appendage o f the cell, termed uropod, and of CXCR4 receptor to the leading edge o f migrating B cells. Time-lapse videomicroscopy studies revealed that SDF-1 alpha-treated cells recruited additional bystander B cells throu gh the uropod. SDF-1 alpha induced levels of cellular recruitment comp arable to those elicited by polarization-inducing anti-ICAM-3 monoclon al antibody, in an LFA-1/ICAM-1, -3-dependent fashion. Moreover, this chemokine increased intracellular Ca2+ levels in B lymphocytes, and in duced a rapid CXCR4 receptor down-regulation on the cell surface membr ane. These results provide new insight into the important biological r ole of SDF-1 alpha in physiological processes in which B cells partici pate, and suggest a key role for chemokines in normal B cell trafficki ng and recirculation.