Immunological gene signatures in B cell follicle reticular cells are highly conserved across organs and species

Abstract Secondary lymphoid organs (SLO) such as the spleen, lymph nodes and Peyer’s patches are strategically positioned to survey bodily surfaces and to support the generation of cellular and humoral immunity. The movement and interaction of antigens, antigen presenting cells, B and T lymphocytes within SLOs is coordinated by specialized fibroblastic reticular cells (FRCs) that form dedicated microenvironments and provide essential niche molecules such as the chemokine CXCL13. High-resolution transcriptomic analysis of Cxcl13-expressing cells in mouse models has previously enabled the molecular characterization of heterogenous B cell-interacting reticular cells (BRC) in lymph nodes. However, it remains unknown to what extent the molecular identity of niche-forming BRCs is conserved across SLOs. Here, we employed single cell RNA-sequencing of Cxcl13-expressing cells from murine lymph node, spleen and Peyer’s patch to compare the molecular identity of BRCs across SLOs. While structural and developmental genes dominated organ-specific gene signatures, we found conserved gene signatures reflecting crucial immunomodulatory functions. The highest conservation was observed in follicular dendritic cells, a BRC subset specialized in the capture and presentation of antigen. Moreover, immunomodulatory gene signatures were preserved in BRCs from human lymph nodes and palatine tonsils highlighting the important role of BRC-defined microenvironments in steering efficient immune responses in SLOs across species.