{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE332nnn/GSE332886/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE332886"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Aire is a cell intrinsic regulator of natural IgM-secreting cells","description":"The Autoimmune Regulator (Aire) serves an essential role in T cell tolerance by promoting ‘promiscuous gene expression’ (PGE) in medullary thymic epithelial cells (mTECs). Several disease manifestations associated with Aire-deficiency, some apparently non-autoimmune, along with Aire expression beyond mTECs, suggest that Aire may regulate additional physiological processes. Here, we show that plasmablasts (PBs) and plasma cells (PCs) constitute a principal Aire-expressing population in the spleen, with highest expression in IgM+ cells and lower levels in class-switched PB/PCs. The Aire+IgM+ PB/PC compartment exhibits typical hallmarks of natural IgM secreting cells of extrafollicular origin: it is T cell-independent, exhibits distinct BCR features, and can originate from both peritoneal B1a cells and splenic marginal zone B cells, whereas follicular B cells may contribute to a lesser extent, at least under homeostatic conditions. While TLR-driven signals are sufficient in vitro to initiate PB differentiation from B1a and marginal zone B cells as previously described, we show that APRIL or BAFF synergize with TLR signaling to induce robust Aire expression, revealing a previously unrecognized TNF superfamily axis controlling Aire induction. Aire does not drive bona fide PGE in these cells, yet cell-intrinsically restrains their numbers, uncovering a role in homeostatic regulation of natural polyreactive IgM in steady state rather than classical maintenance of self-tolerance.","dates":{"publication":"2026/09/01"},"accession":"GSE332886","cross_references":{"GSM":["GSM9754609","GSM9754608","GSM9754612","GSM9754611","GSM9754603","GSM9754614","GSM9754602","GSM9754613","GSM9754616","GSM9754605","GSM9754615","GSM9754604","GSM9754607","GSM9754606","GSM9754610"],"GPL":["16417"],"GSE":["332886"],"taxon":["Mus musculus"]}}