title: Human B cells express the orphan chemokine receptor CRAM-A/B in a maturation-stage-dependent and CCL5-modulated manner.
abstract: Chemokines orchestrate the organization of leucocyte recruitment during inflammation and homeostasis. Despite growing knowledge of chemokine receptors, some orphan chemokine receptors are still not characterized. The gene CCRL2 encodes such a receptor that exists in two splice variants, CRAM-A and CRAM-B. Here, we report that CRAM is expressed by human peripheral blood and bone marrow B cells, and by different B-cell lines dependent on the B-cell maturation stage. Intriguingly, CRAM surface expression on the pre-B-cell lines Nalm6 and G2 is specifically upregulated in response to the inflammatory chemokine CCL5 (RANTES), a chemokine that is well known to play an important role in modulating immune responses. Although Nalm6 cells do not express any of the known CCL5 binding receptors, extracellular signal-regulated kinases 1 and 2 (ERK1/2) are phosphorylated upon CCL5 stimulation, suggesting a direct effect of CCL5 through the CRAM receptor. However, no calcium mobilization or migratory responses upon CCL5 stimulation are induced in B-cell lines or in transfected cells. Also, ERK1/2 phosphorylation cannot be inhibited by pertussis toxin, suggesting that CRAM does not couple to Gi proteins. Our results describe the expression of a novel, non-classical chemokine receptor on B cells that is potentially involved in immunomodulatory functions together with CCL5.
authors.affiliation: Department of Internal Medicine, Freiburg University Clinic, Freiburg, Germany.
authors.forename: Tanja N
authors.initials: TN
authors.lastname: Hartmann
authors.forename: Marion
authors.initials: M
authors.lastname: Leick
authors.forename: Susann
authors.initials: S
authors.lastname: Ewers
authors.forename: Andrea
authors.initials: A
authors.lastname: Diefenbacher
authors.forename: Ingrid
authors.initials: I
authors.lastname: Schraufstatter
authors.forename: Marek
authors.initials: M
authors.lastname: Honczarenko
authors.forename: Meike
authors.initials: M
authors.lastname: Burger
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D020013:Calcium Signaling / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000276:immunology; D054388:Receptors, CCR / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D022502:Stress Fibers / Q000276:immunology
chemical_list: C487531:CCRL2 protein, human; D018946:Chemokine CCL5; D020033:Protein Isoforms; D054388:Receptors, CCR; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3