Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue
More about Open Access at the CrickAuthors list
Lucia Montorsi Michael J Pitcher Yuan Zhao Chiara Dionisi Alicia Demonti Thomas J Tull Pawan Dhami Richard J Ellis Cynthia Bishop Jeremy D Sanderson Sahil Jain David D'Cruz Deena L Gibbons Thomas H Winkler Mats Bemark Francesca Ciccarelli Jo SpencerAbstract
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.
Journal details
Journal
Nature Communications
Volume
15
Issue number
1
Pages
4051
Available online
Publication date
Full text links
Publisher website (DOI)
10.1038/s41467-024-48267-4
Europe PubMed Central
38744839
Pubmed
38744839
Keywords
Related topics
Type of publication
Publishing history
The publication was previously a preprint.
View preprint
