Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/185208
Title: | Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses |
Author: | Rodríguez Ubreva, Javier Arutyunyan, Anna Bonder, Marc Jan Pino Molina, Lucía del Clark, Stephen J. Calle Fabregat, Carlos de la García Alonso, Luz Handfield, Louis François Ciudad, Laura Andrés León, Eduardo Krueger, Felix Català Moll, Francesc Rodríguez Cortez, Virginia C. Polanski, Krzysztof Mamanova, Lira Dongen, Stijn van Kiselev, Vladimir Yu. Martínez Saavedra, María T. Heyn, Holger Martín, Javier Warnatz, Klaus López Granados, Eduardo Rodríguez Gallego, Carlos Stegle, Oliver Kelsey, Gavin Vento Tormo, Roser Ballestar Tarín, Esteban |
Keywords: | Limfòcits Epigenètica Lymphocytes Epigenetics |
Issue Date: | 1-Apr-2022 |
Publisher: | Springer Science and Business Media |
Abstract: | Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency. Here the authors perform single-cell omics analyses in CVID-discordant monozygotic twins and show epigenetic and transcriptional alterations associated with activation in memory B cells. 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 naive-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 naive-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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-022-29450-x |
It is part of: | Nature Communications, 2022 |
URI: | http://hdl.handle.net/2445/185208 |
Related resource: | https://doi.org/10.1038/s41467-022-29450-x |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
s41467-022-29450-x.pdf | 10.08 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License