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, RANK ?CD11c and RANK ?LysM mice were bred and kept in specific pathogen-free conditions. All experiments were carried out in conformity with the animal bioethics legislation and institutional guidelines. To generate mice with conditional RANKL deficiency in marginal reticular cells, Ly5.1 (CD45.1) and RANKL ?Ccl19

, RANKLf/f (B6.129-Tnfsf11tm1.1Caob/J) mice, vol.19

, Unless otherwise indicated all mice were 8 weeks old. To inhibit lymphotoxin, RANKL and TNF pathway, mice received 20 µg of LT?R-muIgG1 (LT?R-Fc , kindly provided by Biogen

. Briefly, Collagenase D (Roche,1mg/ml), DNase I (Roche, 0.1mg/ml) under agitation at 37°C for 1h. The cell suspension was then filtered at 100µm. TER119 and anti-CD45 coupled magnetic beads (Miltenyi Biotec). LN macrophages were isolated following the same protocol as for stromal cells omitting the CD45+ cell depletion step. Flow cytometry and immunofluorescence Primary and secondary antibodies used are listed in Supplemental Table, Flow cytometry was performed on a Gallios (Beckman-Coulter) and analyzed with FlowJo software (Treestar). Cells were sorted on a FACS Aria II

, Eight µm LN and spleen sections were cut on a cryostat (Leica), fixed in cold acetone and blocked with 2% BSA. After immunolabelling, sections were mounted in Fluomount (Dako) and images acquired on a spinning disk inverted microscope (Carl Zeiss) and the appropriate software (Metamorph)

, blood endothelial cells (BEC) and fibroblastic reticular cells (FRC) was extracted using the RNeasy kit (Qiagen) and cDNA was synthesized with Maxima First Strand cDNA Synthesis Kit (Thermo Scientific) and Improm-II (Promega) using oligo(dT)15 primers. RT-PCR was performed using Luminaris color HiGreen qPCR Master Mix (Thermo Scientific) using the following primers to amplify RANK: forward 5'-tgcgtgctgctcgttcca, reverse 5'-accgtccgagatgctcataat with the housekeeping gene coding for GAPDH (Forward 5'-TGACGTGCCGCCTGGAGAAA and Reverse 5'-AGTGTAGCCCAAGATGCCCTTCAG), Quantitative RT-PCR was run on a Bio-Rad CFX96 thermal cycler, and threshold values

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