An atlas of cells in the human tonsil

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.

Keywords:

T FOLLICULAR HELPER

SINGLE-CELL

B-CELLS

GERMINAL CENTER

DENDRITIC CELLS

PLASMA-CELLS

LIGHT-ZONE

DIFFERENTIATION

MOUSE

DISTINCT

An atlas of cells in the human tonsil

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