1. Academic Validation
  2. Human B cell-attracting chemokine 1 (BCA-1; CXCL13) is an agonist for the human CXCR3 receptor

Human B cell-attracting chemokine 1 (BCA-1; CXCL13) is an agonist for the human CXCR3 receptor

  • Cytokine. 2001 Aug 7;15(3):113-21. doi: 10.1006/cyto.2001.0923.
C H Jenh 1 M A Cox W Hipkin T Lu C Pugliese-Sivo W Gonsiorek C C Chou S K Narula P J Zavodny
Affiliations

Affiliation

  • 1 Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. Chung-Her.Jenh@spcorp.com
Abstract

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.

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