Human B cells express the orphan chemokine receptor CRAM-A/B in a maturation-stage-dependent and CCL5-modulated manner.
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.
Hartmann
Tanja N
TN
Department of Internal Medicine, Freiburg University Clinic, Freiburg, Germany.
Leick
Marion
M
Ewers
Susann
S
Diefenbacher
Andrea
A
Schraufstatter
Ingrid
I
Honczarenko
Marek
M
Burger
Meike
M
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
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