title: Follicular dendritic cells emerge from ubiquitous perivascular precursors.
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 β (PDGFRβ). PDGFRβ-Cre-driven reporter gene recombination resulted in FDC labeling, whereas conditional ablation of PDGFRβ(+)-derived cells abolished FDC, indicating that FDC originate from PDGFRβ(+) cells. Lymphotoxin-α-overexpressing prion protein (PrP)(+) kidneys developed PrP(+) FDC after transplantation into PrP(-) mice, confirming that preFDC exist outside lymphoid organs. Adipose tissue-derived PDGFRβ(+) stromal-vascular cells responded to FDC maturation factors and, when transplanted into lymphotoxin β receptor (LTβR)(-) kidney capsules, differentiated into Mfge8(+)CD21/35(+)FcγRIIβ(+)PrP(+) FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte-deficient mice contained perivascular PDGFRβ(+) 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.
authors: Institute of Neuropathology, University Hospital of Zurich, 8091 Zurich, Switzerland.
authors: Nike Julia
authors: NJ
authors: Krautler
authors: Veronika
authors: V
authors: Kana
authors: Jan
authors: J
authors: Kranich
authors: Yinghua
authors: Y
authors: Tian
authors: Dushan
authors: D
authors: Perera
authors: Doreen
authors: D
authors: Lemm
authors: Petra
authors: P
authors: Schwarz
authors: Annika
authors: A
authors: Armulik
authors: Jeffrey L
authors: JL
authors: Browning
authors: Michelle
authors: M
authors: Tallquist
authors: Thorsten
authors: T
authors: Buch
authors: José B
authors: JB
authors: Oliveira-Martins
authors: Caihong
authors: C
authors: Zhu
authors: Mario
authors: M
authors: Hermann
authors: Ulrich
authors: U
authors: Wagner
authors: Robert
authors: R
authors: Brink
authors: Mathias
authors: M
authors: Heikenwalder
authors: Adriano
authors: A
authors: Aguzzi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001808:Blood Vessels / Q000166:cytology*; D020566:Dendritic Cells, Follicular / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
chemical_list: D020797:Receptor, Platelet-Derived Growth Factor beta