Histamine H4 receptor antagonists prevent receptor-mediated and EBV-induced B cell proliferation [ATAC-seq]

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.