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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 beta (PDGFRbeta). PDGFRbeta-Cre-driven reporter gene recombination resulted in FDC labeling, whereas conditional ablation of PDGFRbeta(+)-derived cells abolished FDC, indicating that FDC originate from PDGFRbeta(+) cells. Lymphotoxin-alpha-overexpressing prion protein (PrP)(+) kidneys developed PrP(+) FDC after transplantation into PrP(-) mice, confirming that preFDC exist outside lymphoid organs. Adipose tissue-derived PDGFRbeta(+) stromal-vascular cells responded to FDC maturation factors and, when transplanted into lymphotoxin beta receptor (LTbetaR)(-) kidney capsules, differentiated into Mfge8(+)CD21/35(+)FcgammaRIIbeta(+)PrP(+) FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte-deficient mice contained perivascular PDGFRbeta(+) 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:

Type Journal
Authors Krautler, N. J.; Kana, V.; Kranich, J.; Tian, Y.; Perera, D.; Lemm, D.; Schwarz, P.; Armulik, A.; Browning, J. L.; Tallquist, M.; Buch, T.; Oliveira-Martins, J. B.; Zhu, C.; Hermann, M.; Wagner, U.; Brink, R.; Heikenwalder, M.; Aguzzi, A.
Garvan Authors Prof Robert Brink
Publisher Name CELL
Published Date 2012-07-06 00:00:00
Published Volume 150
Published Issue 1
Published Pages 194-206
URL http://www.ncbi.nlm.nih.gov/pubmed/22770220
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?11391_11887/2012.Krautler.Cell.pdf