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DC Field | Value | Language |
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dc.contributor.author | Pino Molina, Lucía del | - |
dc.contributor.author | Rodríguez Ubreva, Javier | - |
dc.contributor.author | Torres Canizales, Juan | - |
dc.contributor.author | Coronel Díaz, María | - |
dc.contributor.author | Kulis, Marta | - |
dc.contributor.author | Martín-Subero, José Ignacio | - |
dc.contributor.author | van der Burg, Mirjam | - |
dc.contributor.author | Ballestar Tarín, Esteban | - |
dc.contributor.author | López Granados, Eduardo | - |
dc.date.accessioned | 2020-10-27T11:59:34Z | - |
dc.date.available | 2020-10-27T11:59:34Z | - |
dc.date.issued | 2019-04-24 | - |
dc.identifier.uri | http://hdl.handle.net/2445/171562 | - |
dc.description.abstract | Common Variable Immunodeficiency (CVID) is characterized by impaired antibody production and poor terminal differentiation of the B cell compartment, yet its pathogenesis is still poorly understood. We first reported the occurrence of epigenetic alterations in CVID by high-throughput methylation analysis in CVID-discordant monozygotic twins. Data from a recent whole DNA methylome analysis throughout different stages of normal B cell differentiation allowed us to design a new experimental approach. We selected CpG sites for analysis based on two criteria: one, CpGs with potential association with the transcriptional status of relevant genes for B cell activation and differentiation; and two, CpGs that undergo significant demethylation from naive to memory B cells in healthy individuals. DNA methylation was analyzed by bisulfite pyrosequencing of specific CpG sites in sorted naive and memory B cell subsets from CVID patients and healthy donors. We observed impaired demethylation in two thirds of the selected CpGs in CVID memory B cells, in genes that govern B cell-specific processes or participate in B cell signaling. The degree of demethylation impairment associated with the extent of the memory B cell reduction. The impaired demethylation in such functionally relevant genes as AICDA in switched memory B cells correlated with a lower proliferative rate. Our new results reinforce the hypothesis of altered demethylation during B cell differentiation as a contributing pathogenic mechanism to the impairment of B cell function and maturation in CVID. In particular, deregulated epigenetic control of AICDA could play a role in the defective establishment of a post-germinal center B cell compartment in CVID. | - |
dc.format.extent | 11 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Frontiers Media Sa | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2019.00878 | - |
dc.relation.ispartof | Frontiers in Immunology, 2019, vol. 10 | - |
dc.relation.uri | https://doi.org/10.3389/fimmu.2019.00878 | - |
dc.rights | cc by (c) Pino Molina et al., 2019 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | - |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Malalties immunològiques | - |
dc.subject.classification | Cèl·lules B | - |
dc.subject.other | Immunologic diseases | - |
dc.subject.other | B cells | - |
dc.title | Impaired CpG Demethylation in Common Variable Immunodeficiency Associates With B Cell Phenotype and Proliferation Rate | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2020-10-26T09:21:44Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 31105700 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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File | Description | Size | Format | |
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del Pino-MolinaL.pdf | 3.26 MB | Adobe PDF | View/Open |
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