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Significance The CD169 + macrophages that play an important role in the fight against infections and cancer are receptive to environmental signals for their differentiation. We show that lymph node and splenic CD169 + macrophages require both LTβR and RANK signaling since the conditional deficiency of either receptor results in their disappearance. Using a reporter mouse, we observe RANKL expression by a splenic mesenchymal cell subset and show that it participates in CD169 + macrophage differentiation. Their absence leads to a reduced viral capture and a greatly attenuated virus-specific CD8 + T cell expansion. Thus, tight control mechanisms operate for the precise positioning of these macrophages at sites where numerous immune-stimulatory forces converge.
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Camara et al. (2022) studied this question.
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