title: Early CCR6 expression on B cells modulates germinal centre kinetics and efficient antibody responses.
abstract: The CC-chemokine receptor 6 (CCR6) can be detected on naive and activated B cells. Counterintuitively, its absence accelerates the appearance of germinal centres (GCs) and increases the production of low-affinity antibodies. The detailed mechanism of CCR6 function during the humoral response has remained elusive, but previously we identified a distinct CCR6highB-cell population in vivo early after antigenic challenge. In this study, we defined this population specifically as early, activated pre-GC B cells. In accordance, we show that CCR6 is upregulated rapidly within hours on the protein or mRNA level after activation in vitro. In addition, only activated B cells migrated specifically towards CCL20, the specific ligand for CCR6. Lack of CCR6 increased the dark zone/light zone ratio of GC and led to decreased antigen-specific IgG1 and IgG2a antibody generation in a B-cell intrinsic manner in mixed bone marrow chimeras. In contrast, antigen-specific IgM responses were normal. Hence, CCR6 negatively regulates entry of activated, antigen-specific pre-GC B cells into the GC reaction.
authors.affiliation: Division of Molecular Immunology, Internal Medicine III, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Reimer
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.|Royal Hobart Hospital, Hobart, Tasmania, Australia.
authors.forename: Adrian Ys
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bannan
authors.affiliation: ANZAC Research Institute, Concord Hospital, Sydney, New South Wale, Australia.
authors.forename: Phillip
authors.initials: P
authors.lastname: Fromm
authors.affiliation: School of Molecular and Biomedical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Ervin E
authors.initials: EE
authors.lastname: Kara
authors.affiliation: School of Molecular and Biomedical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Iain
authors.initials: I
authors.lastname: Comerford
authors.affiliation: School of Molecular and Biomedical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Shaun
authors.initials: S
authors.lastname: McColl
authors.affiliation: Cellular Signalling and Human Disease Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Florian
authors.initials: F
authors.lastname: Wiede
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Dirk
authors.initials: D
authors.lastname: Mielenz
authors.affiliation: Division of Molecular Immunology, Internal Medicine III, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Körner
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D054418:Chemokine CCL20 / Q000494:pharmacology; D005434:Flow Cytometry; D018858:Germinal Center / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D054418:Chemokine CCL20; D012333:RNA, Messenger; D054399:Receptors, CCR6