Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an understanding of the functional units of the tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer as locally active in follicle-associated T and B cells, and identified SIX5 as putative transcriptional regulator of plasma cell maturation. Analyses of a validation cohort confirmed the presence, annotation, and markers of tonsillar cell types and provided evidence of age-related compositional shifts. We demonstrate the value of this resource by annotating cells from B cell-derived mantle cell lymphomas, linking transcriptional heterogeneity to normal B cell differentiation states of the human tonsil.

腭扁桃体是次级淋巴器官 (SLO)，代表针对吸入或摄入病原体的第一道免疫防御线。我们生成了由超过 556,000 个细胞组成的人类扁桃体图谱，这些细胞通过五种不同的数据模式进行分析，包括单细胞转录组、表观基因组、蛋白质组和免疫组库测序以及空间转录组学。这次普查确定了 121 种细​​胞类型和状态，定义了发育轨迹，并使人们能够了解扁桃体的功能单位。举例来说，我们对骨髓 slan 样亚型进行了分层，建立了在滤泡相关 T 和 B 细胞中具有局部活性的BCL6增强子，并将 SIX5 鉴定为浆细胞成熟的推定转录调节因子。对验证队列的分析证实了扁桃体细胞类型的存在、注释和标记，并提供了与年龄相关的成分变化的证据。我们通过注释 B 细胞衍生的套细胞淋巴瘤的细胞，将转录异质性与人扁桃体的正常 B 细胞分化状态联系起来，证明了该资源的价值。