{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300663/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300663"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Histamine H4 receptor antagonists prevent receptor-mediated and EBV-induced B cell proliferation [ATAC-seq]","description":"Epstein-Barr virus (EBV) infects over 90% of the global population and establishes lifelong latency in memory B cells. In healthy individuals, this latent infection is typically kept in check by the immune system. However, in immunosuppressed patients, EBV can reactivate, leading to uncontrolled B cell proliferation and development of post-transplant lymphoproliferative disorders (PTLD)—a potentially fatal complication. In this study, we demonstrate that selective antagonists of the histamine H4 receptor (H4R), a G protein-coupled receptor expressed in immune cells, potently suppress B cell activation and proliferation triggered by antigenic stimuli or EBV infection. Notably, the lead compound A943931 inhibited transcriptional programs critical for B cell activation, including downregulation of key metabolic genes, resulting in profound suppression of both glycolysis and oxidative phosphorylation. A943931 also blocked EBV-driven B cell immortalization and impaired energy metabolism in lymphoblastoid cell lines, albeit to a lesser extent than in receptor-stimulated B cells. In vivo, A943931 suppressed tumor growth in Daudi Burkitt lymphoma xenografts and prevented B cell lymphoma development in EBV-infected humanized mice. These findings reveal a novel immunometabolic vulnerability of EBV-infected B cells and position H4R antagonists as promising therapeutic candidates for EBV-associated lymphoproliferative disorders, including PTLD and potentially EBV-linked autoimmune diseases.","dates":{"publication":"2026/06/29"},"accession":"GSE300663","cross_references":{"GSM":["GSM9065937","GSM9065926","GSM9065927","GSM9065938","GSM9065924","GSM9065935","GSM9065936","GSM9065925","GSM9065933","GSM9065934","GSM9065923","GSM9065942","GSM9065931","GSM9065932","GSM9065939","GSM9065928","GSM9065929","GSM9065940","GSM9065941","GSM9065930"],"GPL":["18573"],"GSE":["300663"],"taxon":["Homo sapiens"],"PMID":["[42140525]"]}}