Single cell RNAseq of B cell interacting reticular cells and immune cells from murine secondary lymphoid organs

B cell-interacting reticular cells (BRC) form transcriptionally and topologically stable immune-interacting microenvironments that direct efficient humoral immunity. While several immune niche factors have been elucidated, the cues sustaining BRC function and topology across activation states remain unclear. Here, we employed single cell RNA-sequencing of stromal cells and immune cells from murine lymph nodes, Peyer's patches and spleens to analyse local BRC-immune cell interactions and compare them across SLOs and species. Shared BRC subsets were imprinted by tissue-specific gene signatures, but also expressed functionally convergent niche factors that directed regionalized leukocyte composition. Local BRC-immune cell interactions sustained BRC subset identity via immune cell-provided maturation factors. Bidirectional signalling programs were independent of activation state and mirrored across murine and human tissues. Collectively, our data reveal a conserved set of feedforward BRC-immune cell circuits that sustain topologically-organized, functional niches across inflammatory states, lymphoid organs and species.B细胞相互作用网状细胞（B cell-interacting reticular cells, BRC）可形成转录与拓扑结构均稳定的免疫相互微环境，介导高效的体液免疫应答。尽管目前已阐明多种免疫微环境调控因子，但维持BRC功能与拓扑结构随激活状态变化的信号机制仍不明确。本研究对小鼠淋巴结、派尔集合淋巴结及脾脏中的基质细胞与免疫细胞开展单细胞RNA测序（single cell RNA-sequencing），以此分析局部BRC与免疫细胞的相互作用，并在次级淋巴器官（secondary lymphoid organs, SLOs）及不同物种间进行比较。研究发现，跨组织共有BRC亚群受组织特异性基因特征调控，同时表达功能趋同的微环境因子，这些因子可调控区域化的白细胞组成。局部BRC与免疫细胞的相互作用可通过免疫细胞提供的成熟因子维持BRC亚群的身份特征。双向信号通路程序不受激活状态影响，且在小鼠与人类组织中均存在保守的对应模式。综上，本研究数据揭示了一套保守的前馈式BRC-免疫细胞环路，该环路可在炎症状态、不同淋巴器官及跨物种间维持拓扑结构有序的功能性免疫微环境。