Human B cell-attracting chemokine 1 (BCA-1; CXCL13) is an agonist for the human CXCR3 receptor.
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 (Burkitt'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 BLR1/CXCR5 receptor is sufficient to disrupt organization of follicles in spleen and Peyer's patches, BCA-1 may act as a B cell homing chemokine. Nonetheless, BCA-1 has not been tested against all known chemokine receptors. In this study, we report that human BCA-1 competes with radiolabeled interferon gamma (IFN-gamma) inducible protein 10 (IP-10) for binding to the human CXCR3 receptor expressed in Ba/F3 and 293EBNA cell lines. 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 CXCR3. 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 induced by IP-10. In addition, human BCA-1 is an agonist in stimulating GTP gamma S 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 recent 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.
Jenh
C H
CH
Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. Chung-Her.Jenh@spcorp.com
Cox
M A
MA
Hipkin
W
W
Lu
T
T
Pugliese-Sivo
C
C
Gonsiorek
W
W
Chou
C C
CC
Narula
S K
SK
Zavodny
P J
PJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D054357:Chemokine CXCL10; D054382:Chemokine CXCL13; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism* / Q000502:physiology*; D002633:Chemotaxis; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008024:Ligands; D051379:Mice; D011485:Protein Binding; D051381:Rats; D054367:Receptors, CXCR3; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000819:agonists*; D018121:Receptors, Cytokine / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D000911:Antibodies, Monoclonal; C110663:CXCL13 protein, human; C515187:CXCR3 protein, human; C095085:CXCR5 protein, human; C513179:CXCR5 protein, mouse; D054357:Chemokine CXCL10; D054382:Chemokine CXCL13; D018925:Chemokines; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; C515188:Cxcr3 protein, mouse; C515189:Cxcr3 protein, rat; D018076:DNA, Complementary; D008024:Ligands; D054367:Receptors, CXCR3; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D007371:Interferon-gamma; D002118:Calcium