title: Dendritic cells and monocyte/macrophages that create the IL-6/APRIL-rich lymph node microenvironments where plasmablasts mature.
abstract: IL-6 and APRIL influence the growth, differentiation, and survival of normal and neoplastic Ab-forming cells (AFC). In this study, we identify two subsets of myeloid cells that associate with the AFC and are the main producers of these factors during a T-dependent Ab response to alum-precipitated protein in mouse lymph nodes. First CD11c(+)CD8alpha(-) dendritic cells located in the perivascular area of the T zone provide about half of the IL-6 mRNA produced in the node together with significant amounts of APRIL mRNA. The number of these cells increases during the response, at least in part due to local proliferation. The second subset comprises Gr1(+)CD11b(+)F4/80(+) monocyte/macrophages. These colonize the medullary cords during the response and are the other main IL-6 mRNA producers and the greatest source of APRIL mRNA. This medullary cord monocyte/macrophage subset results in local increase of APRIL mRNA that mirrors the polarity of CXCL12 expression in the node. The distribution of these myeloid cell subsets correlates with a gradient of AFC maturation assessed by progressive loss of Ki67 as AFC pass from the B cell follicle along the perivascular areas to the medullary cords.
authors.affiliation: Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom. e.mohr@bham.ac.uk
authors.forename: Elodie
authors.initials: E
authors.lastname: Mohr
authors.forename: Karine
authors.initials: K
authors.lastname: Serre
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Manz
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.forename: Mahmood
authors.initials: M
authors.lastname: Khan
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Hardie
authors.forename: Roger
authors.initials: R
authors.lastname: Bird
authors.forename: Ian C M
authors.initials: IC
authors.lastname: MacLennan
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005434:Flow Cytometry; D015850:Interleukin-6 / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D042282:Microdissection; D018613:Microscopy, Confocal; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13