Human B cells become highly responsive to macrophage-inflammatory protein-3 alpha/CC chemokine ligand-20 after cellular activation without changes in CCR6 expression or ligand binding.
CCR6 is the only known receptor for the chemokine macrophage-inflammatory protein (MIP)-3alpha/CC chemokine ligand (CCL)20. We have shown previously that CCR6 is expressed on peripheral blood B cells, but CCR6 activity on these cells is low in in vitro assays. We report that MIP-3alpha/CCL20-induced calcium flux and chemotaxis can be enhanced significantly on peripheral blood and tonsillar B cells after activation by cross-linking surface Ag receptors. Of particular interest is the fact that the enhanced activity on B cells was not associated with an increase in CCR6 expression as assessed by levels of receptor mRNA, surface staining, or MIP-3alpha/CCL20 binding sites, or by a change in the affinity of the receptor for ligand. These data convincingly demonstrate that responses to a chemokine can be regulated solely by changes in the downstream pathways for signal transduction resulting from Ag receptor activation, and establish CCR6 as an efficacious receptor on human B cells.
Liao
Fang
F
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Shirakawa
Aiko-Konno
AK
Foley
John F
JF
Rabin
Ronald L
RL
Farber
Joshua M
JM
D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001665:Binding Sites / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000378:metabolism* / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003432:Cross-Linking Reagents / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007399:Interphase / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D003432:Cross-Linking Reagents; D008024:Ligands; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D002118:Calcium