Development of follicular dendritic cells in lymph nodes depends on retinoic acid mediated signaling

Specialized stromal cells occupy and help define B- and T cell domains, which is crucial for proper functioning of our immune system. Signaling through lymphotoxin and TNF-receptors is crucial for development of different stromal subsets which are thought to arise from a common precursor. However, mechanisms that control the selective generation of the different stromal phenotypes are not known. Here we show that in mice, retinoic acid mediated signaling is important for the differentiation of precursors towards the Cxcl13 pos follicular dendritic cell (FDC) lineage, while blocking lymphotoxin mediated Ccl19 pos fibroblastic reticular cell (FRC) lineage differentiation. Consequently, we see at day of birth Cxcl13 pos Ccl19 neg/low and Cxcl13 neg/low Ccl19 pos cells within neonatal lymph nodes. Furthermore, ablation of retinoic acid receptor signaling in stromal precursors early after birth reduces Cxcl13 expression, while in addition, complete blockade of retinoic acid signaling prevents formation of FDC networks in lymph nodes.