Collections / Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue

Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue

Intestinal homeostasis is maintained by the response of gut-associated lymphoid tissue to bacteria transported across the follicle associated epithelium into the subepithelial dome. The initial response to antigens and how bacteria are handled is incompletely understood. By iterative application of spatial transcriptomics and multiplexed single-cell technologies, we identify that the double negative 2 subset of B cells, previously associated with autoimmune diseases, is present in the subepithelial dome in health. We show that in this location double negative 2 B cells interact with dendritic cells co-expressing the lupus autoantigens DNASE1L3 and C1q and microbicides. We observe that in humans, but not in mice, dendritic cells expressing DNASE1L3 are associated with sampled bacteria but not DNA derived from apoptotic cells. We propose that fundamental features of autoimmune diseases are microbiota-associated, interacting components of normal intestinal immunity.

Datasets2
Size~28 MB
AssayVisium
Samplehuman · gut-associated lymphoid tissue
KindOther
PMID:38744839 ↗
Python · lamindb
import lamindb as ln
import spatialdata as sd

coll = ln.Collection.get(key="geo-gse251693")
coll.ordered_artifacts.df()                 # the 2 members, ordered

# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]

# …or load each straight into memory as a SpatialData object:
sdatas = {a.key: sd.read_zarr(a.cache()) for a in coll.ordered_artifacts.all()}
Open in Vitessce
Visium
Human gut-associated lymphoid tissue
GSM7986081
human gut-associated lymphoid tissue 18 MB 3,408 obs bronze H&E
TechnologyVisium
Organismhuman
Tissuegut-associated lymphoid tissue
Size18 MB
Obs3,408
Magnificationother · 3.476 µm/px
bronze H&E Open in Vitessce
Open in Vitessce
Visium
Human gut-associated lymphoid tissue
GSM7986082
human gut-associated lymphoid tissue 10.0 MB 2,351 obs bronze H&E
TechnologyVisium
Organismhuman
Tissuegut-associated lymphoid tissue
Size10.0 MB
Obs2,351
Magnificationother · 3.345 µm/px
bronze H&E Open in Vitessce

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