Optimal AID expression and efficient immunoglobulin class switch recombination are dependent on the Hypoxia-Inducible Factor.
Fiche publication
Date publication
mai 2023
Journal
European journal of immunology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr REINA-SAN-MARTIN Bernardo
Tous les auteurs :
Heyer V, Reina-San-Martin B
Lien Pubmed
Résumé
During immune responses, B cells engaging a cognate antigen are recruited to germinal centers in secondary lymphoid organs where they will diversify their B cell receptor (BCR) to generate highly specific and adapted humoral responses. They do so, by inducing the expression of Activation induced cytidine deaminase (AID), which initiates Somatic Hypermutation (SHM) and Class Switch Recombination (CSR). AID deaminates cytosines in single stranded DNA, generating U:G mismatches that are processed to inducing double stranded DNA break intermediates during CSR that result in the expression of a different antibody isotype. Interestingly, Hypoxia regions have been reported in germinal centers and suggesting that hypoxia could modulate the humoral response. Furthermore, Hypoxia Inducible transcription Factor (HIF) can bind to the AID promoter and induce AID expression in a non-B cell setting, suggesting that it might be involved in the transcriptional induction of AID in B cells, hence regulating SHM and CSR. We thus hypothesized that HIF could regulate the efficiency of CSR. Here we show that the inactivation of both the HIF-1α and HIF-1β subunits of the HIF transcription factor in murine CH12 B cells results in defective CSR and that this is due to the suboptimal induction of AID expression. This article is protected by copyright. All rights reserved.
Mots clés
AID, B cell receptor, HIF-1α, HIF-1β, class switch recombination
Référence
Eur J Immunol. 2023 05 4;:e2350373