Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/178643
Title: Activation-induced deaminase is critical for the establishment of DNA methylation patterns prior to the germinal center reaction
Author: Català Moll, Francesc
Ferreté Bonastre, Anna G.
Li, Tianlu
Weichenhan, Dieter
Lutsik, Pavlo
Ciudad, Laura
Álvarez Prado, Ángel F.
Rodríguez Ubreva, Javier
Klemann, Christian
Speckmann, Carsten
Vilas Zornoza, Amaya
Abolhassani, Hassan
Martínez Gallo, Mónica
Dieli Crimi, Romina
Rivière, Jacques G.
Martín Nalda, Andrea
Colobran, Roger
Soler Palacín, Pere
Kracker, Sven
Hammarström, Lennart
Prosper, Felipe
Durandy, Anne
Grimbacher, Bodo
Plass, Christoph
Ballestar Tarín, Esteban
Keywords: ADN
Metilació
Cèl·lules B
DNA
Methylation
B cells
Issue Date: 5-May-2021
Publisher: Oxford University Press
Abstract: Activation-induced deaminase (AID) initiates antibody diversification in germinal center B cells by deaminating cytosines, leading to somatic hypermutation and class-switch recombination. Loss-of-function mutations in AID lead to hyper-IgM syndrome type 2 (HIGM2), a rare human primary antibody deficiency. AID-mediated deamination has been proposed as leading to active demethylation of 5-methycytosines in the DNA, although evidence both supports and casts doubt on such a role. In this study, using whole-genome bisulfite sequencing of HIGM2 B cells, we investigated direct AID involvement in active DNA demethylation. HIGM2 naïve and memory B cells both display widespread DNA methylation alterations, of which ∼25% are attributable to active DNA demethylation. For genes that undergo active demethylation that is impaired in HIGM2 individuals, our analysis indicates that AID is not directly involved. We demonstrate that the widespread alterations in the DNA methylation and expression profiles of HIGM2 naïve B cells result from premature overstimulation of the B-cell receptor prior to the germinal center reaction. Our data support a role for AID in B cell central tolerance in preventing the expansion of autoreactive cell clones, affecting the correct establishment of DNA methylation patterns.
Note: Reproducció del document publicat a: https://doi.org/10.1093/nar/gkab322
It is part of: Nucleic Acids Research, 2021, vol. 49, num. 9, p. 5057-5073
URI: http://hdl.handle.net/2445/178643
Related resource: https://doi.org/10.1093/nar/gkab322
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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