title: The dendritic cell-specific CC-chemokine DC-CK1 is expressed by germinal center dendritic cells and attracts CD38-negative mantle zone B lymphocytes.
abstract: DC-CK1 (CCL18) is a dendritic cell (DC)-specific chemokine expressed in both T and B cell areas of secondary lymphoid organs that preferentially attracts CD45RA(+) T cells. In this study, we further explored the nature of DC-CK1 expressing cells in germinal centers (GCs) of secondary lymphoid organs using a newly developed anti-DC-CK1 mAb. Immunohistochemical analysis demonstrated a remarkable difference in the number of DC-CK1 expressing cells in adjacent GCs within one tonsil, implicating that the expression of DC-CK1 in GCs depends on the activation and/or progression stage of the GC reaction. Using immunohistology and RNA analysis, we demonstrated that GCDC are the source of DC-CK1 production in the GCs. Considering the recently described function of GCDC in (naive) B cell proliferation, isotype switching and Ab production, we investigated the ability of DC-CK1 to attract B lymphocytes. Here we demonstrate that DC-CK1 is a pertussis toxin-dependent chemoattractant for B lymphocytes with a preference in attracting mantle zone (CD38(-)) B cells. The findings that GCDC produce DC-CK1 and attract mantle zone B cells support a key role for GCDC in the development of GCs and memory B cell formation.
authors.affiliation: Department of Tumor Immunology, University Medical Center, Nijmegen, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Lindhout
authors.forename: J L
authors.initials: JL
authors.lastname: Vissers
authors.forename: F C
authors.initials: FC
authors.lastname: Hartgers
authors.forename: R J
authors.initials: RJ
authors.lastname: Huijbens
authors.forename: N M
authors.initials: NM
authors.lastname: Scharenborg
authors.forename: C G
authors.initials: CG
authors.lastname: Figdor
authors.forename: G J
authors.initials: GJ
authors.lastname: Adema
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D019742:Chemokines, CC / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002648:Child; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000096:biosynthesis*; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; C111792:CCL18 protein, human; D019742:Chemokines, CC; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1