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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Keyword

Animals

Humans

Mice

B-Lymphocytes/immunology

Gastrointestinal Microbiome/immunology

Endodeoxyribonucleases/metabolism

Dendritic Cells/immunology

Lymphoid Tissue/immunology

Female

Mice, Inbred C57BL

Intestinal Mucosa/immunology

Male

Publication and Content Type

art (subject category)

ref (subject category)