GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300663/primary200OKGenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300663GEOGSEfalseHistamine H4 receptor antagonists prevent receptor-mediated and EBV-induced B cell proliferation [ATAC-seq]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.2026/06/29GSE300663GSM9065937GSM9065926GSM9065927GSM9065938GSM9065924GSM9065935GSM9065936GSM9065925GSM9065933GSM9065934GSM9065923GSM9065942GSM9065931GSM9065932GSM9065939GSM9065928GSM9065929GSM9065940GSM9065941GSM906593018573300663Homo sapiens[42140525]