Rodríguez Ubreva, JavierHeyn, HolgerBallestar, Esteban2022-05-312022-05-312022Rodríguez-Ubreva J, Arutyunyan A, Jan Bonder M, Del Pino-Molina L, Clark SJ, de la Calle-Fabregat C. et al. Single-cell atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses. Nat Commun. 2022 Apr 1;13(1):1779. DOI:10.1038/s41467-022-29450-x2041-1723http://hdl.handle.net/10230/53327Common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, displays impaired terminal B-cell differentiation and defective antibody responses. Incomplete genetic penetrance and ample phenotypic expressivity in CVID suggest the participation of additional pathogenic mechanisms. Monozygotic (MZ) twins discordant for CVID are uniquely valuable for studying the contribution of epigenetics to the disease. Here, we generate a single-cell epigenomics and transcriptomics census of naïve-to-memory B cell differentiation in a CVID-discordant MZ twin pair. Our analysis identifies DNA methylation, chromatin accessibility and transcriptional defects in memory B-cells mirroring defective cell-cell communication upon activation. These findings are validated in a cohort of CVID patients and healthy donors. Our findings provide a comprehensive multi-omics map of alterations in naïve-to-memory B-cell transition in CVID and indicate links between the epigenome and immune cell cross-talk. Our resource, publicly available at the Human Cell Atlas, gives insight into future diagnosis and treatments of CVID patients.application/pdfeng© Javier Rodríguez-Ubreva et al. 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were madeEpigenèticaEpigenòmicaImmunodeficiènciaMalaltiesinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-022-29450-xinfo:eu-repo/semantics/openAccess