Optimal AID expression and efficient immunoglobulin class switch recombination are dependent on the hypoxia-inducible factor.
AID
B cell receptor
HIF-1α
HIF-1β
class switch recombination
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
revised:
31
03
2023
received:
12
01
2023
accepted:
02
05
2023
medline:
17
7
2023
pubmed:
5
5
2023
entrez:
5
5
2023
Statut:
ppublish
Résumé
During immune responses, B cells engaging a cognate antigen are recruited to GCs in secondary lymphoid organs where they will diversify their 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 ss DNA, generating U:G mismatches that are processed to induce ds DNA break intermediates during CSR that result in the expression of a different antibody isotype. Interestingly, hypoxia regions have been reported in GCs 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.
Identifiants
pubmed: 37143384
doi: 10.1002/eji.202350373
doi:
Substances chimiques
Cytidine Deaminase
EC 3.5.4.5
Immunoglobulin Isotypes
0
Transcription Factors
0
AICDA (activation-induced cytidine deaminase)
EC 3.5.4.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2350373Subventions
Organisme : IdEx Unistra
ID : ANR-10-IDEX-0002
Organisme : SFRI-STRAT'US project
ID : ANR 20-SFRI-0012
Organisme : EUR IMCBio
ID : ANR-17-EURE-0023
Informations de copyright
© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
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