<p>G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [<cite idref="PUB00004961"/>]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/). </p><p>The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7transmembrane (TM) helices [<cite idref="PUB00000131"/>, <cite idref="PUB00002477"/>, <cite idref="PUB00004960"/>].</p><p>Chemokines are proteins that have important physiological and patho- physiological roles in a wide range of acute and chronic inflammatory processes. Their sequences are similar and are characterised by a 4-cysteine motif: the family can be divided according to whether the first 2Cys residues are adjacent (the C-C family), or separated by an interveningresidue (the C-x-C family).</p><p>A novel C-X-C chemokine, named B cell-attracting chemokine 1 (BCA-1), wasidentified through screening of expressed sequence tag data [<cite idref="PUB00007112"/>]. The chemokine was found to be expressed at highest levels in the liver, spleen, lymph nodes, appendix and stomach. Lower levels of BCA-1 were also found in the salivary and mammary glands. Expression appears to be constitutive in lymphoid tissues.</p><p>The receptor for BCA-1 was found to be a previously identified orphan receptor, expressed on B lymphocytes and Burkitt's lymphoma cells. This receptor, originally named BLR1 (Burkitt's lymphoma receptor 1), has nowbeen renamed CXCR5 (C-X-C chemokine receptor type 5) [<cite idref="PUB00007112"/>]. B lymphocytes expressing CXCR5 migrate in a concentration dependent manner in response to BCA-1. BCA-1 does not induce chemotaxis in T lymphocytes, monocytes or neutrophils. This selectivity for B lymphocytes is unique among the chemokines. BCA-l/CXCR5 may be important for the development of B cell areas of secondary lymphoid tissue; deletion of the CXCR5 gene in mice results in animals lacking inguinal lymph nodes and having defective formation of primary follicles and germinal centres of the spleen and Peyer's patches. Receptor-deficient B cells enter T cell areas but do not migrate into B cell areas. The expression of CXCR5 in Burkitt's lymphoma cells also suggests a role for the receptor in lymphomagenesis [<cite idref="PUB00001477"/>].</p> CXC chemokine receptor, type 5