title: Fibrinogen is localized on dark zone follicular dendritic cells in vivo and enhances the proliferation and survival of a centroblastic cell line in vitro.
abstract: Follicular dendritic cells (FDC) in the germinal centers (GC) of secondary lymphoid organs increase the survival and proliferation of antigen-stimulated B cells and are pivotal for the affinity maturation of an antibody response and for maintenance of B cell immunological memory. The dark zone (DZ) and the light zone (LZ) constitute distinct areas of the GC containing different subtypes of FDC as identified by their morphology and phenotype. Until now, most available FDC-specific reagents identify LZ FDC, and there are no reagents recognizing DZ FDC specifically. Here, we report a new mAb, D46, which stains FDC specifically in the DZ of bovine and ovine GC within the secondary follicles. We identify its ligand as bovine fibrinogen, and using commercially available anti-human fibrinogen antibodies, show that this inflammatory protein is also present on DZ FDC of human GC within palatine tonsils. In vitro, the addition of exogenous fibrinogen stimulates the proliferation and survival of BCR-stimulated L3055 cells, which constitute a clonal population of centroblastic cells and retain important features of normal GC B cells. Together, our results suggest that fibrinogen localized on DZ FDC could support the extensive proliferation and survival of GC B cells within the DZ in vivo.
authors.affiliation: Compton Laboratory, Institute for Animal Health, High Street, Compton, near Newbury, Berkshire RG20 7NN, UK. eric.lefevre@bbsrc.ac.uk
authors.forename: Eric A
authors.initials: EA
authors.lastname: Lefevre
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Hein
authors.forename: Zania
authors.initials: Z
authors.lastname: Stamataki
authors.forename: Louise S
authors.initials: LS
authors.lastname: Brackenbury
authors.forename: Emma A
authors.initials: EA
authors.lastname: Supple
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hunt
authors.forename: Paul
authors.initials: P
authors.lastname: Monaghan
authors.forename: Gwenoline
authors.initials: G
authors.lastname: Borhis
authors.forename: Yolande
authors.initials: Y
authors.lastname: Richard
authors.forename: Bryan
authors.initials: B
authors.lastname: Charleston
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002051:Burkitt Lymphoma / Q000276:immunology / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology; D002417:Cattle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology*; D020566:Dendritic Cells, Follicular / Q000378:metabolism*; D005340:Fibrinogen / Q000502:physiology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D012756:Sheep; D015398:Signal Transduction; D013601:T-Lymphocytes; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D016692:Receptors, Antigen, T-Cell, gamma-delta; D005340:Fibrinogen