Single-cell atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses

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• dc.contributor.author Rodríguez Ubreva, Javier
• dc.contributor.author Heyn, Holger
• dc.contributor.author Ballestar, Esteban
• dc.date.accessioned 2022-05-31T09:59:49Z
• dc.date.available 2022-05-31T09:59:49Z
• dc.date.issued 2022
• dc.description.abstract Common 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.
• dc.description.sponsorship This study was funded by: Spanish Ministry of Science and Innovation (grant number PID2020-117212RB-I00/AEI/10.13038/501100011033) (E.B.), Instituto de Salud Carlos III (ISCIII), Ref. AC18/00057, associated with i-PAD project (ERARE European Union program) (E.B.), Wellcome Sanger core funding (grant no. WT206194) (R.V.-T.), the Chan Zuckerberg Initiative (grant 2020-216799) (R.V.-T. and E.B.), an EMBO short-term fellowship (J.R.U.), Fondo de Investigación Sanitaria Instituto de Salud Carlos III (FIS PI16/01605) (L.P.-M.), the Spanish Ministry of Science, Innovation and Universities (SAF2017-89109-P; AEI/FEDER, UE) (H.H.), Instituto de Salud Carlos III, Ministry of Health (PI16/00759) and European Regional Development Fund-European Social Fund—FEDER-FSE) (C.R-G.), Grupo DISA (OA18/017) (C.R.-G.), the UK Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0426) (G.K.) and Medical Research Council (MR/S000437/1) (G.K.)
• dc.format.mimetype application/pdf
• dc.identifier.citation Rodríguez-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-x
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-022-29450-x
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/53327
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-89109-P
• dc.rights © 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 made
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other Epigenètica
• dc.subject.other Epigenòmica
• dc.subject.other Immunodeficiència
• dc.subject.other Malalties
• dc.title Single-cell atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion