ArticleThe Journal of biological chemistry2010
Estrogen receptors bind to and activate the HOXC4/HoxC4 promoter to potentiate HoxC4-mediated activation-induced cytosine deaminase induction, immunoglobulin class switch DNA recombination, and somatic hypermutation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 85 citations in OpenAlex.
- Immunogenicity of trivalent inactivated influenza vaccination received during pregnancy or postpartum.Obstetrics and gynecology · 2012Trial
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- Association between sex hormones and innate cytotoxic capacity of circulating and rectal mucosal immune cells.Clinical immunology communications · 2026Article
- B Cell Tolerance and Obstetric Antiphospholipid Syndrome.Clinical reviews in allergy & immunology · 2025Review
- Sex Differences in Immune Responses to Infectious Diseases: The Role of Genetics, Hormones, and Aging.Diseases (Basel, Switzerland) · 2025Review
- Estrogen influences class-switched memory B cell frequency only in humans with two X chromosomes.The Journal of experimental medicine · 2025Article
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- A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses.Nature immunology · 2024Article
- A humanized mouse that mounts specific and mature antibody and autoantibody responses.Nature immunology · 2024Article
- Isoform-specific knockdown of long and intermediate prolactin receptors interferes with evolution of B-cell neoplasms.Communications biology · 2023Article
- Sex chromosome complement and sex steroid signaling underlie sex differences in immunity to respiratory virus infection.Frontiers in pharmacology · 2023Review
- The NFκB signaling system in the generation of B-cell subsets: from germinal center B cells to memory B cells and plasma cells.Frontiers in immunology · 2023Review
- Gender-Diverse Inclusion in Immunological Research: Benefits to Science and Health.Frontiers in medicine · 2022Review
- SARS-Cov2 S Protein Features Potential Estrogen Binding Site.Food technology and biotechnology · 2021Article
- From Influenza Virus Infections to Lupus: Synchronous Estrogen ReceptorViral immunology · 2020Article
- Estrogen Reverses HDAC Inhibitor-Mediated Repression ofFrontiers in immunology · 2020Article
- Aneuploidy and a deregulated DNA damage response suggest haploinsufficiency in breast tissues ofScience advances · 2020Article
- Recent Advances in Lupus B Cell Biology: PI3K, IFNγ, and Chromatin.Frontiers in immunology · 2020Review
- Matters of life and death: How estrogen and estrogen receptor binding to the immunoglobulin heavy chain locus may influence outcomes of infection, allergy, and autoimmune disease.Cellular immunology · 2019Review
- Frontline Science: A reduction in DHA-derived mediators in male obesity contributes toward defects in select B cell subsets and circulating antibody.Journal of leukocyte biology · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Estrogen enhances antibody and autoantibody responses through yet to be defined mechanisms. It has been suggested that estrogen up-regulates the expression of activation-induced cytosine deaminase (AID), which is critical for antibody class switch DNA recombination (CSR) and somatic hypermutation (SHM), through direct activation of this gene. AID, as we have shown, is induced by the HoxC4 homeodomain transcription factor, which binds to a conserved HoxC4/Oct site in the AICDA/Aicda promoter. Here we show that estrogen-estrogen receptor (ER) complexes do not directly activate the AID gene promoter in B cells undergoing CSR. Rather, they bind to three evolutionarily conserved and cooperative estrogen response elements (EREs) we identified in the HOXC4/HoxC4 promoter. By binding to these EREs, ERs synergized with CD154 or LPS and IL-4 signaling to up-regulate HoxC4 expression, thereby inducing AID and CSR without affecting B cell proliferation or plasmacytoid differentiation. Estrogen administration in vivo significantly potentiated CSR and SHM in the specific antibody response to the 4-hydroxy-3-nitrophenylacetyl hapten conjugated with chicken γ-globulin. Ablation of HoxC4 (HoxC4(-/-)) abrogated the estrogen-mediated enhancement of AID gene expression and decreased CSR and SHM. Thus, estrogen enhances AID expression by activating the HOXC4/HoxC4 promoter and inducing the critical AID gene activator, HoxC4.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.