The chemokine receptor CXCR3 is expressed on malignant B cells and mediates chemotaxis

B- and T-cell recirculation is crucial for the function of the immune syste m, with the control of cell migration being mainly mediated by several chem okines and their receptors. In this study, we investigated the expression a nd function of CXCR3 on normal and malignant B cells from 65 patients with chronic lymphoproliferative disorders (CLDs). Although CXCR3 is lacking on CD5(+) and CD5(-) B cells from healthy subjects, it is expressed on leukemi c B lymphocytes from all (31/31) patients with chronic lymphocytic leukemia (CLL). The presence of CXCR3 was heterogeneous in other B-cell disorders, being expressed in 2 of 7 patients with mantle cell lymphoma (MCL), 4 of 12 patients with hairy cell leukemia (HCL), and 11 of 15 patients with other subtypes of non-Hodgkin's lymphomas (NHLs). Chemotaxis assay shows that nor mal B cells From healthy subjects do not migrate in response to IFN-inducib le protein 10 (IP-10) and IFN-gamma-induced monokine (:Mig). In contrast, a definite migration in response to IP-10 and Mig has been observed in all m alignant B cells from patients with CLL, but not in patients with HCL or MC L (1/7 cases tested). Neoplastic B cells from other NHLs showed a heterogen ous pattern. The migration elicited by IP-10 and Mig was inhibited by block ing CXCR3. No effect of IP-10 and Mig chemokines was observed on the cytoso lic calcium concentration in malignant B cells. The data reported here demo nstrate that CXCR3 is expressed on malignant B cells from CLDs, particularl y in patients with CLL, and represents a fully functional receptor involved in chemotaxis of malignant B lymphocytes.