{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318206/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318206"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Transcriptomic Characterisation of Transitional B Cells Reveals Four Subsets with Perturbed Activation Profiles in Systemic Sclerosis","description":"We have previously shown that patients with systemic sclerosis (SSc) exhibit increased frequencies of autoreactive transitional B cells, including those with anti-topoisomerase I (ATA+) specificity, an autoantibody associated with progressive interstitial lung disease. This suggests that defective transitional B cell tolerance drives autoimmunity in SSc, however, the mechanism underpinning reduced censorship of these early B cells remains undefined. To investigate this, we applied single-cell transcriptomic and B cell receptor (BCR) sequencing to dissect the molecular and repertoire features of transitional B cells isolated from early-stage ATA+ treatment-naive SSc patients. This revealed four distinct transitional B cell clusters: T1, T2, CD27+ and marginal zone precursors (MZP). Novel marker genes were identified within these clusters, including the pro-apoptotic gene HRK which was specifically enriched in the MZP cluster. These findings were validated using a publicly available single-cell dataset. Among these transitional clusters, T1 B cells were significantly expanded in SSc patients, with a two-fold increase compared with matched healthy controls, suggesting elevated bone marrow output or increased exodus of transitional B cells in SSc. Additionally, pro-survival genes such as IL4R, TCL1A and S100A10 were significantly upregulated in SSc, whilst a key negative regulator of PI3K/AKT signalling, FOX01 was significantly reduced. Interferon responsive genes (IFITM1 and IFITM2) were also significantly increased in SSc transitional B cells, consistent with dysregulated interferon signalling in SSc. BCR analysis revealed significantly increased CDR3 hydrophobicity in SSc, notably in the T2 cluster, where a trend towards increased usage of the autoimmunity-associated gene IGHV4-39 was also observed. Furthermore, the κ/λ light chain ratio was elevated in the majority of SSc patients, perhaps implying incomplete receptor editing. Collectively, our findings support divergent transitional B cell development and activation in SSc, with an AKT-driven pathway likely promoting autoreactive transitional B cell survival.","dates":{"publication":"2026/08/14"},"accession":"GSE318206","cross_references":{"GSM":["GSM9489279","GSM9489289","GSM9489278","GSM9489277","GSM9489288","GSM9489287","GSM9489276","GSM9489286","GSM9489275","GSM9489285","GSM9489274","GSM9489284","GSM9489273","GSM9489272","GSM9489294","GSM9489283","GSM9489293","GSM9489271","GSM9489282","GSM9489281","GSM9489292","GSM9489291","GSM9489280","GSM9489290"],"GPL":["24676"],"GSE":["318206"],"taxon":["Homo sapiens"]}}