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Brief Definitive Reports

Daniel F. Legler^*, Marcel Loetscher^*, Regula Stuber Roos^*, Ian Clark-Lewis, Marco Baggiolini^*, and Bernhard Moser^*

From the ^* Theodor-Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland, and the Biomedical Research Center, University of British Columbia, Vancouver, BC V6T 1Z3 Canada

Although most leukocytes, T lymphocytes in particular, respond to several different chemokines, there is virtually no information on chemokine activities and chemokine receptors in B lymphocytes. A putative chemokine receptor, BLR1, that is expressed in Burkitt's lymphoma cells and B lymphocytes was cloned a few years ago. Deletion of the gene for BLR1 yielded mice with abnormal primary follicles and germinal centers of the spleen and Peyer's patches, reflecting the inability of B lymphocytes to migrate into B cell areas. By screening expressed sequence tag DNA sequences, we have identified a CXC chemokine, termed B cell–attracting chemokine 1 (BCA-1), that is chemotactic for human B lymphocytes. BCA-1 cDNA encodes a protein of 109 amino acids with a leader sequence of 22 residues. The mature protein shares 23–34% identical amino acids with known CXC chemokines and is constitutively expressed in secondary lymphoid organs. BCA-1 was chemically synthesized and tested for activity on murine pre–B cells 300-19 transfected with BLR1 and on human blood B lymphocytes. In transfected cells, BCA-1 induced chemotaxis and Ca²⁺ mobilization demonstrating that it acts via BLR1. Under the same conditions, no activity was obtained with 10 CXC and 19 CC chemokines, lymphotactin, neurotactin/fractalkine and several other peptide ligands. BCA-1 was also a highly effective attractant for human blood B lymphocytes (which express BLR1), but was inactive on freshly isolated or IL-2–stimulated T lymphocytes, monocytes, and neutrophils. In agreement with the nomenclature rules for chemokine receptors, we propose the term CXCR5 for BLR1. Together with the observed disturbance of B cell colonization in BLR1/ CXCR5-deficient mice, the present results indicate that chemotactic recruitment by locally produced BCA-1 is important for the development of B cell areas of secondary lymphoid tissues.

This work was supported by grant 31-39744.93 of the Swiss National Science Fundation to M. Baggiolini and B. Moser, and the Protein Engineering Network of Centers of Excellence (PENCE), Canada (to I. Clark-Lewis). The Professor Max Cloëtta Foundation, Zürich, supports B. Moser with a career development award.

Address correspondence to Marco Baggiolini, Theodor-Kocher Institute, University of Bern, PO Box 99, CH-3000 Bern 9, Switzerland. Phone: 41-31-631-4141; Fax: 41-31-631-3799; E-mail: marco.baggiolini{at}tki.unibe.ch

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