ArticleInternational immunology2019
Complex sex-biased antibody responses: estrogen receptors bind estrogen response elements centered within immunoglobulin heavy chain gene enhancers.
Article in International immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 3 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- [Gender-specific differences in outcome and survival in early cystectomy : Systematic review].Urologie (Heidelberg, Germany) · 2026Pooled it
- Sex-specific differences in recurrence and progression following cytostatic intravesical chemotherapy for non-muscle invasive urothelial bladder cancer (NMIBC).Journal of cancer research and clinical oncology · 2025Pooled it
- Impact of menopause on relapse rate and disability level in patients with multiple sclerosis (MS): a systematic review and meta-analysis.BMC neurology · 2023Pooled it
- Sex differences in the chronic autoimmune response to myocardial infarction.Clinical science (London, England : 1979) · 2025Article
- Estrogen influences class-switched memory B cell frequency only in humans with two X chromosomes.The Journal of experimental medicine · 2025Article
- Sexual Size Dimorphism Correlates With the Number of Androgen Response Elements in Mammals, But Only in Small-Bodied Species.Genome biology and evolution · 2025Article
- Article
- Article
- How Estrogen, Testosterone, and Sex Differences Influence Serum Immunoglobulin Isotype Patterns in Mice and Humans.Viruses · 2023Article
- Evolutive emergence and divergence of an Ig regulatory node: An environmental sensor getting cues from the aryl hydrocarbon receptor?Frontiers in immunology · 2023Review
- Microbiome Shapes the T Cell Receptor Repertoire among CD4+CD8+ Thymocytes.Biomedicines · 2022Article
- Retinol Binding Protein, Sunlight Hours, and the Influenza Virus-Specific Immune Response.Biomedicines · 2022Article
- Article
- Immunoglobulin G Is Increased in the Injured Spinal Cord in a Sex- and Age-Dependent Manner.Journal of neurotrauma · 2022Article
- Gender-Diverse Inclusion in Immunological Research: Benefits to Science and Health.Frontiers in medicine · 2022Review
- Sex bias in lymphocytes: Implications for autoimmune diseases.Frontiers in immunology · 2022Review
- Immunoglobulin germline gene variation and its impact on human disease.Genes and immunity · 2021Review
- Sendai Virus-Vectored Vaccines That Express Envelope Glycoproteins of Respiratory Viruses.Viruses · 2021Review
- Effect of Vitamin A Deficiency in Dysregulating Immune Responses to Influenza Virus and Increasing Mortality Rates After Bacterial Coinfections.The Journal of infectious diseases · 2021Article
- A Case of Double Standard: Sex Differences in Multiple Sclerosis Risk Factors.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Nuclear hormone receptors including the estrogen receptor (ERα) and the retinoic acid receptor regulate a plethora of biological functions including reproduction, circulation and immunity. To understand how estrogen and other nuclear hormones influence antibody production, we characterized total serum antibody isotypes in female and male mice of C57BL/6J, BALB/cJ and C3H/HeJ mouse strains. Antibody levels were higher in females compared to males in all strains and there was a female preference for IgG2b production. Sex-biased patterns were influenced by vitamin levels, and by antigen specificity toward influenza virus or pneumococcus antigens. To help explain sex biases, we examined the direct effects of estrogen on immunoglobulin heavy chain sterile transcript production among purified, lipopolysaccharide-stimulated B cells. Supplemental estrogen in B-cell cultures significantly increased immunoglobulin heavy chain sterile transcripts. Chromatin immunoprecipitation analyses of activated B cells identified significant ERα binding to estrogen response elements (EREs) centered within enhancer elements of the immunoglobulin heavy chain locus, including the Eµ enhancer and hypersensitive site 1,2 (HS1,2) in the 3' regulatory region. The ERE in HS1,2 was conserved across animal species, and in humans marked a site of polymorphism associated with the estrogen-augmented autoimmune disease, lupus. Taken together, the results highlight: (i) the important targets of ERα in regulatory regions of the immunoglobulin heavy chain locus that influence antibody production, and (ii) the complexity of mechanisms by which estrogen instructs sex-biased antibody production profiles.
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Registered trials
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.