Author:
Braikia Fatima-Zohra,Oudinet Chloé,Haddad Dania,Oruc Zeliha,Orlando Domenico,Dauba Audrey,Le Bert Marc,Khamlichi Ahmed Amine
Abstract
Class switch recombination (CSR) plays an important role in adaptive immune response by enabling mature B cells to switch from IgM expression to the expression of downstream isotypes. CSR is preceded by inducible germline (GL) transcription of the constant genes and is controlled by the 3′ regulatory region (3′RR) in a stimulus-dependent manner. Why the 3′RR-mediated up-regulation of GL transcription is delayed to the mature B-cell stage is presently unknown. Here we show that mice devoid of an inducible CTCF binding element, located in the α constant gene, display a marked isotype-specific increase of GL transcription in developing and resting splenic B cells and altered CSR in activated B cells. Moreover, insertion of a GL promoter downstream of the CTCF insulator led to premature activation of the ectopic promoter. This study provides functional evidence that the 3′RR has a developmentally controlled potential to constitutively activate GL promoters but that this activity is delayed, at least in part, by the CTCF insulator, which borders a transcriptionally active domain established by the 3′RR in developing B cells.
Funder
Institut National du Cancer
Agence Nationale de la Recherche
Association pour la Recherche sur le Cancer
Ligue Contre le Cancer
Publisher
Proceedings of the National Academy of Sciences
Cited by
19 articles.
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