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

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 pathog...

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Detalles Bibliográficos
Autores: Rodríguez-Ubreva, Javier|||0000-0003-4707-4536, Arutyunyan, Anna, Bonder, Marc Jan, Del Pino Molina, Lucía|||0000-0003-2392-097X, Clark, Stephen J.|||0000-0002-6183-491X, de la Calle-Fabregat, Carlos|||0000-0002-3026-3069, Garcia-Alonso, Luz|||0000-0002-7863-9619, Handfield, Louis-François, Ciudad, Laura|||0000-0002-5219-6792, Andrés-León, Eduardo|||0000-0002-0621-9914, Krueger, Felix|||0000-0002-5513-3324, Català-Moll, Francesc|||0000-0002-2354-8648, Rodríguez-Cortez, Virginia C., Polanski, Krzysztof, Mamanova, Lira, van Dongen, Stijn, Kiselev, Vladimir Yu, Martínez-Saavedra, María T.|||0000-0001-8579-226X, Heyn, Holger|||0000-0002-3276-1889, Martín, Javier|||0000-0002-2202-0622, Warnatz, Klaus|||0000-0002-1172-865X, López-Granados, Eduardo, Rodríguez-Gallego, Carlos|||0000-0002-4344-8644, Stegle, Oliver|||0000-0002-8818-7193, Kelsey, Gavin|||0000-0002-9762-5634, Vento Tormo, Roser|||0000-0002-9870-8474, Ballestar, Esteban|||0000-0002-1400-2440
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:270631
Acceso en línea:https://ddd.uab.cat/record/270631
https://dx.doi.org/urn:doi:10.1038/s41467-022-29450-x
Access Level:acceso abierto
Palabra clave:B-Lymphocytes
Common Variable Immunodeficiency
Epigenesis, Genetic
Epigenomics
Germinal Center
Humans
Descripción
Sumario: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.

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