title: Clonal Proliferation and Stochastic Pruning Orchestrate Lymph Node Vasculature Remodeling.
abstract: Lymph node (LN) expansion during an immune response relies on the transient remodeling of its vasculature. Although the mechanisms driving LN endothelial cell division are beginning to be understood, a comprehensive view of LN endothelial cell dynamics at the single-cell level is lacking. Here, we used multicolored fluorescent fate-mapping models to track the behavior of blood endothelial cells during LN expansion upon inflammation and subsequent return to homeostasis. We found that expansion of the LN vasculature relied on the sequential assembly of endothelial cell proliferative units. This segmented growth was sustained by the clonal proliferation of high endothelial venule (HEV) cells, which act as local progenitors to create capillaries and HEV neo-vessels at the periphery of the LN. Return to homeostasis was accompanied by the stochastic death of pre-existing and neo-synthesized LN endothelial cells. Thus, our fate-mapping studies unravel-at a single-cell level-the complex dynamics of vascular-tree remodeling during LN expansion and contraction.
authors.affiliation: Aix-Marseille Université, CNRS, INSERM, CIML, 13288 Marseille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mondor
authors.affiliation: Aix-Marseille Université, CNRS, INSERM, CIML, 13288 Marseille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Jorquera
authors.affiliation: Aix-Marseille Université, CNRS, INSERM, CIML, 13288 Marseille, France.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Sene
authors.affiliation: INSERM U905, 76183 Rouen, France; Normandie University, Institute for Research and Innovation in Biomedicine, 76183 Rouen, France.
authors.forename: Sahil
authors.initials: S
authors.lastname: Adriouch
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany; Faculty of Medicine, University of Muenster, 48149 Muenster, Germany.
authors.forename: Ralf Heinrich
authors.initials: RH
authors.lastname: Adams
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Wienert
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Frederick
authors.initials: F
authors.lastname: Klauschen
authors.affiliation: Aix-Marseille Université, CNRS, INSERM, CIML, 13288 Marseille, France. Electronic address: bajenoff@ciml.univ-mrs.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Bajénoff
mesh_terms: D000818:Animals; D002196:Capillaries / Q000276:immunology / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology* / Q000502:physiology*; D006706:Homeostasis / Q000276:immunology / Q000502:physiology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000502:physiology*; D051379:Mice