Follicular Dendritic Cells Emerge from Ubiquitous Perivascular Precursors

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 (PDGFR beta). PDGFR beta-Cre-driven reporter gene recombination resulted inFDClabeling, whereas conditional ablation of PDGFR beta(+)-derived cells abolished FDC, indicating that FDC originate from PDGFR beta(+) 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 PDGFR beta(+) stromal-vascular cells responded to FDC maturation factors and, when transplanted into lymphotoxin b receptor (LT beta R)(-) kidney capsules, differentiated into Mfge8(+)CD21/35(+) Fc gamma RII beta+PrP+FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte-deficient mice contained perivascular PDGFRb + 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.