1. Follicular Dendritic Cells Emerge from Ubiquitous Perivascular Precursors
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Annika Armulik, Caihong Zhu, Jan Kranich, Michelle D. Tallquist, Ulrich Wagner, Thorsten Buch, José B. Oliveira-Martins, Veronika Kana, Robert Brink, Nike Julia Krautler, Mathias Heikenwalder, Petra Schwarz, Dushan Perera, Yinghua Tian, Mario Hermann, Jeffrey L. Browning, Doreen Lemm, Adriano Aguzzi, University of Zurich, and Aguzzi, Adriano
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10208 Institute of Neuropathology ,610 Medicine & health ,Spleen ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Receptor, Platelet-Derived Growth Factor beta ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Growth factor receptor ,1300 General Biochemistry, Genetics and Molecular Biology ,medicine ,Animals ,10217 Clinic for Visceral and Transplantation Surgery ,030304 developmental biology ,Inflammation ,B-Lymphocytes ,0303 health sciences ,Follicular dendritic cells ,Biochemistry, Genetics and Molecular Biology(all) ,Stem Cells ,Germinal center ,Germinal Center ,Molecular biology ,Specific Pathogen-Free Organisms ,Killer Cells, Natural ,Transplantation ,medicine.anatomical_structure ,Lymphatic system ,Lymphotoxin ,Immunology ,570 Life sciences ,biology ,Blood Vessels ,Stem cell ,Dendritic Cells, Follicular ,030215 immunology - Abstract
The differentiation of follicular dendritic cells (FDC) is essential to the remarkable microanatomic plasticity of lymphoid follicles. Here we show that FDC arise from ubiquitous perivascular precursors (preFDC) expressing platelet derived growth factor receptor ß (PDGFRß). PDGFRß Cre driven reporter gene recombination resulted in FDC labeling whereas conditional ablation of PDGFRß+ derived cells abolished FDC indicating that FDC originate from PDGFRß+ cells. Lymphotoxin a overexpressing prion protein (PrP)+ kidneys developed PrP+ FDC after transplantation into PrP mice confirming that preFDC exist outside lymphoid organs. Adipose tissue derived PDGFRß+ stromal vascular cells responded to FDC maturation factors and when transplanted into lymphotoxin ß receptor (LTßR) kidney capsules differentiated into Mfge8+CD21/35 +Fc?RIIß+PrP+ FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte deficient mice contained perivascular PDGFRß+ FDC precursors whose expansion required both lymphoid tissue inducer (LTi) cells and lymphotoxin. The ubiquity of preFDC and their strategic location at blood vessels may explain the de novo generation of organized lymphoid tissue at sites of lymphocytic inflammation. PaperFlick: © 2012 Elsevier Inc.
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