Author/Authors :
Nike Julia Krautler، نويسنده , , Veronika Kana، نويسنده , , Jan Kranich، نويسنده , , Yinghua Tian، نويسنده , , Dushan Perera، نويسنده , , Doreen Lemm، نويسنده , , Petra Schwarz، نويسنده , , Annika Armulik، نويسنده , , Jeffrey L. Browning، نويسنده , , Michelle Tallquist، نويسنده , , Thorsten Buch، نويسنده , , José B. Oliveira-Martins، نويسنده , , Caihong Zhu، نويسنده , , Mario Hermann، نويسنده , , Ulrich Wagner، نويسنده , , Robert Brink، نويسنده , , Mathias Heikenwalder، نويسنده , , Adriano Aguzzi، نويسنده ,
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.
