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

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 immunodef...

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Detalles Bibliográficos
Autores: 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 Carolina, 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/185208
Acceso en línea:https://hdl.handle.net/2445/185208
Access Level:acceso abierto
Palabra clave:Limfòcits
Epigenètica
Lymphocytes
Epigenetics
Descripción
Sumario: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.

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