The CXC chemokine CXCL13, known as BCA-1 (B cell-attracting chemokine 1) or
BLC (B-lymphocyte chemoattractant), has been identified as an efficacious
attractant selective for B lymphocytes. The chemokine receptor BLR1 (Burkit
t's lymphoma receptor 1)/CXCR5 expressed by all mature B cells has to date
been identified as the only known receptor for BCA-1. As the loss of the BL
R1/CXCR5 receptor is sufficient to disrupt organization of follicles in spl
een and Peyer's patches, BCA-1 may act as a B cell homing chemokine. Noneth
eless, BCA-1 has not been tested against all known chemokine receptors. In
this study, we report that human BCA-1 competes with radiolabeled interfero
n gamma (IFN-gamma) inducible protein 10 (IP-10) for binding to the human C
XCR3 receptor expressed in Ba/F3 and 293EBNA cell fines. Furthermore, human
BCA-1 is an efficacious attractant for human CXCR3 transfected cells; BCA-
1-induced chemotaxis is inhibited by a monoclonal antibody against human CX
CR3. In these cells, as in human B lymphocytes expressing CXCR5, BCA-1 does
not induce a calcium flux. Indeed, BCA-1 attenuates the calcium flux induc
ed by IP-10. In addition, human BCA-1 is an agonist in stimulating GTP gamm
aS binding. Together these data suggest that human BCA-1 is a specific and
functional G-protein-linked chemotactic ligand for the human CXCR3 receptor
. The biological significance of this new finding is supported by our recen
t observation that human BCA-1 induces chemotaxis of activated T cells and
the BCA-1-induced chemotaxis is inhibited by a monoclonal antibody against
human CXCR3. (C) 2001 Academic Press.