Clonal Proliferation and Stochastic Pruning Orchestrate Lymph Node Vasculature Remodeling

• Published in: Immunity (Cambridge, Mass.) Mass.), 2016-10, Vol.45 (4), p.877-888
• Main Authors: Mondor, Isabelle, Jorquera, Audrey, Sene, Cynthia, Adriouch, Sahil, Adams, Ralf Heinrich, Zhou, Bin, Wienert, Stephan, Klauschen, Frederick, Bajénoff, Marc
• Format: Article
• Language: English
• Subjects: Animals; Capillaries - immunology; Capillaries - physiology; Cell Proliferation - physiology; Cells, Cultured; Endothelial Cells - immunology; Endothelial Cells - physiology; Homeostasis - immunology; Homeostasis - physiology; Immunology; Inflammation - immunology; Inflammation - pathology; Life Sciences; Lymph Nodes - immunology; Lymph Nodes - physiology; Lymphatic system; Medical imaging; Mice; Rodents; Studies
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2016.09.017

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. [Display omitted] •Expansion of the LN vasculature relies on endothelial cell proliferative units (EPUs)•EPUs are generated by the clonal proliferation of LN-resident endothelial cells•High endothelial venule cells act as endothelial cell progenitors•Return to LN homeostasis relies on the stochastic elimination of endothelial cells How individual endothelial cells cooperate to remodel the lymph node vasculature during an immune response is unclear. Mondor et al. demonstrate that the expansion of the lymph node vasculature relies on the sequential assembly of endothelial cell proliferative units originating from the clonal division of high endothelial venules.