Lymphoid stromal cells (LSCs) are essential organizers of immune responses. We analyzed tonsillar tissue by combining flow cytometry, in situ imaging, RNA sequencing, and functional assays, defining three distinct human LSC subsets. The integrin CD49a designated perivascular stromal cells exhibiting features of local committed LSC precursors and segregated cytokine and chemokine-producing fibroblastic reticular cells (FRCs) supporting B and T cell survival. The follicular dendritic cell transcriptional profile reflected active responses to B cell and non-B cell stimuli. We therefore examined the effect of B cell stimuli on LSCs in follicular lymphoma (FL). FL B cells interacted primarily with CD49a⁺ FRCs. Transcriptional analyses revealed LSC reprogramming in situ downstream of the cytokines tumor necrosis factor (TNF) and transforming growth factor β (TGF-β), including increased expression of the chemokines CCL19 and CCL21. Our findings define human LSC populations in healthy tissue and reveal bidirectional crosstalk between LSCs and malignant B cells that may present a targetable axis in lymphoma.

淋巴基质细胞 (LSC) 是免疫反应的重要组织者。我们通过结合流式细胞术、原位成像、RNA 测序和功能测定来分析扁桃体组织，定义了三个不同的人类 LSC 亚群。整合素 CD49a 指定血管周围基质细胞表现出局部定向 LSC 前体和分离的细胞因子和产生趋化因子的成纤维细胞网状细胞 (FRC) 的特征，支持 B 和 T 细胞存活。滤泡树突细胞转录谱反映了对 B 细胞和非 B 细胞刺激的积极反应。因此，我们检查了 B 细胞刺激对滤泡性淋巴瘤 (FL) 中 LSC 的影响。FL B 细胞主要与 CD49a ⁺ FRC相互作用。转录分析显示 LSC原位重编程细胞因子肿瘤坏死因子 (TNF) 和转化生长因子 β (TGF-β) 的下游，包括趋化因子 CCL19 和 CCL21 的表达增加。我们的研究结果定义了健康组织中的人类 LSC 群体，并揭示了 LSC 和恶性 B 细胞之间的双向串扰，这可能在淋巴瘤中呈现出可靶向的轴。