{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T20:19:12Z","timestamp":1785442752635,"version":"3.56.0"},"reference-count":122,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T00:00:00Z","timestamp":1541635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA21765"],"award-info":[{"award-number":["CA21765"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nuclear hormone receptors including the estrogen receptor (ER\u03b1) 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 ER\u03b1 binding to estrogen response elements (EREs) centered within enhancer elements of the immunoglobulin heavy chain locus, including the E\u00b5 enhancer and hypersensitive site 1,2 (HS1,2) in the 3\u2032 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 ER\u03b1 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.<\/jats:p>","DOI":"10.1093\/intimm\/dxy074","type":"journal-article","created":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T21:14:46Z","timestamp":1541193286000},"page":"141-156","source":"Crossref","is-referenced-by-count":49,"title":["Complex sex-biased antibody responses: estrogen receptors bind estrogen response elements centered within immunoglobulin heavy chain gene enhancers"],"prefix":"10.1093","volume":"31","author":[{"given":"Bart G","family":"Jones","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Danny Thomas Place, Memphis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E","family":"Sealy","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Danny Thomas Place, Memphis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5317-1055","authenticated-orcid":false,"given":"Rhiannon R","family":"Penkert","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Danny Thomas Place, Memphis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherri L","family":"Surman","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Danny Thomas Place, Memphis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W","family":"Maul","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoff","family":"Neale","sequence":"additional","affiliation":[{"name":"Hartwell Center for Bioinformatics & Biotechnology, St. Jude Children\u2019s Research Hospital, Memphis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beisi","family":"Xu","sequence":"additional","affiliation":[{"name":"Computational Biology, St. Jude Children\u2019s Research Hospital, Memphis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J","family":"Gearhart","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia L","family":"Hurwitz","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Danny Thomas Place, Memphis, USA"},{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,11,8]]},"reference":[{"key":"2022071009460347200_CIT0001","doi-asserted-by":"crossref","first-page":"4879","DOI":"10.1038\/ncomms5879","article-title":"Steroid hormone signalling links reproduction to lifespan in dietary-restricted Caenorhabditis elegans","volume":"5","author":"Thondamal","year":"2014","journal-title":"Nat. Commun"},{"key":"2022071009460347200_CIT0002","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.bbadis.2010.12.020","article-title":"The thyroid hormones and their nuclear receptors in the gut: from developmental biology to cancer","volume":"1812","author":"Sirakov","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"2022071009460347200_CIT0003","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nrendo.2017.12","article-title":"The effects of oestrogens and their receptors on cardiometabolic health","volume":"13","author":"Morselli","year":"2017","journal-title":"Nat. Rev. Endocrinol"},{"key":"2022071009460347200_CIT0004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cbf.3086","article-title":"The role of nuclear hormone receptors in cutaneous wound repair","volume":"33","author":"Rieger","year":"2015","journal-title":"Cell Biochem. Funct"},{"key":"2022071009460347200_CIT0005","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.molmet.2014.05.007","article-title":"ER\u03b1 upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue","volume":"3","author":"Kim","year":"2014","journal-title":"Mol. Metab"},{"key":"2022071009460347200_CIT0006","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1093\/nar\/29.14.2905","article-title":"Estrogen receptor interaction with estrogen response elements","volume":"29","author":"Klinge","year":"2001","journal-title":"Nucleic Acids Res"},{"key":"2022071009460347200_CIT0007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0960-0760(99)00124-7","article-title":"Role of estrogen receptor ligand and estrogen response element sequence on interaction with chicken ovalbumin upstream promoter transcription factor (COUP-TF)","volume":"71","author":"Klinge","year":"1999","journal-title":"J. Steroid Biochem. Mol. Biol"},{"key":"2022071009460347200_CIT0008","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1093\/nar\/gkp1188","article-title":"Location analysis for the estrogen receptor-alpha reveals binding to diverse ERE sequences and widespread binding within repetitive DNA elements","volume":"38","author":"Mason","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2022071009460347200_CIT0009","doi-asserted-by":"crossref","first-page":"e87","DOI":"10.1371\/journal.pgen.0030087","article-title":"Whole-genome cartography of estrogen receptor alpha binding sites","volume":"3","author":"Lin","year":"2007","journal-title":"PLoS Genet"},{"key":"2022071009460347200_CIT0010","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/msb.2010.109","article-title":"Integrative model of genomic factors for determining binding site selection by estrogen receptor-\u03b1","volume":"6","author":"Joseph","year":"2010","journal-title":"Mol. Syst. Biol"},{"key":"2022071009460347200_CIT0011","doi-asserted-by":"crossref","first-page":"4458","DOI":"10.1016\/S0021-9258(17)41801-1","article-title":"Phosphorylation of the human estrogen receptor. Identification of hormone-regulated sites and examination of their influence on transcriptional activity","volume":"269","author":"Le Goff","year":"1994","journal-title":"J. Biol. Chem"},{"key":"2022071009460347200_CIT0012","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1615\/CritRevEukaryotGeneExpr.v15.i1.40","article-title":"Nuclear transport of steroid hormone receptors","volume":"15","author":"Shank","year":"2005","journal-title":"Crit. Rev. Eukaryot. Gene Expr"},{"key":"2022071009460347200_CIT0013","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1600-0854.2005.00270.x","article-title":"Mechanisms of receptor-mediated nuclear import and nuclear export","volume":"6","author":"Pemberton","year":"2005","journal-title":"Traffic"},{"key":"2022071009460347200_CIT0014","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1161\/01.RES.0000057753.57106.0B","article-title":"Shear stress causes nuclear localization of endothelial glucocorticoid receptor and expression from the GRE promoter","volume":"92","author":"Ji","year":"2003","journal-title":"Circ. Res"},{"key":"2022071009460347200_CIT0015","doi-asserted-by":"crossref","first-page":"12425","DOI":"10.1074\/jbc.M202752200","article-title":"Dynamic shuttling and intranuclear mobility of nuclear hormone receptors","volume":"278","author":"Maruvada","year":"2003","journal-title":"J. Biol. Chem"},{"key":"2022071009460347200_CIT0016","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1042\/bse0400089","article-title":"Gene repression by nuclear hormone receptors","volume":"40","author":"Moehren","year":"2004","journal-title":"Essays Biochem"},{"key":"2022071009460347200_CIT0017","doi-asserted-by":"crossref","first-page":"3999","DOI":"10.1073\/pnas.96.7.3999","article-title":"Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta","volume":"96","author":"Paige","year":"1999","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2022071009460347200_CIT0018","first-page":"1193","article-title":"Novel estrogen response elements identified by genetic selection in yeast are differentially responsive to estrogens and antiestrogens in mammalian cells","volume":"8","author":"Dana","year":"1994","journal-title":"Mol. Endocrinol"},{"key":"2022071009460347200_CIT0019","first-page":"659","article-title":"Analysis of estrogen receptor function in vitro reveals three distinct classes of antiestrogens","volume":"9","author":"McDonnell","year":"1995","journal-title":"Mol. Endocrinol"},{"key":"2022071009460347200_CIT0020","first-page":"1266","article-title":"Transcriptional activation by the estrogen receptor requires a conformational change in the ligand binding domain","volume":"7","author":"Beekman","year":"1993","journal-title":"Mol. Endocrinol"},{"key":"2022071009460347200_CIT0021","doi-asserted-by":"crossref","first-page":"e1002077","DOI":"10.1371\/journal.pcbi.1002077","article-title":"The role of response elements organization in transcription factor selectivity: the IFN-\u03b2 enhanceosome example","volume":"7","author":"Pan","year":"2011","journal-title":"PLoS Comput. Biol"},{"key":"2022071009460347200_CIT0022","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1038\/nsmb1109-1118","article-title":"How do transcription factors select specific binding sites in the genome","volume":"16","author":"Pan","year":"2009","journal-title":"Nat. Struct. Mol. Biol"},{"key":"2022071009460347200_CIT0023","first-page":"5977","article-title":"Effects of estrogen on global gene expression: identification of novel targets of estrogen action","volume":"60","author":"Charpentier","year":"2000","journal-title":"Cancer Res"},{"key":"2022071009460347200_CIT0024","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1677\/JOE-09-0054","article-title":"Differential induction of LRP16 by liganded and unliganded estrogen receptor alpha in SKOV3 ovarian carcinoma cells","volume":"202","author":"Tian","year":"2009","journal-title":"J. Endocrinol"},{"key":"2022071009460347200_CIT0025","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/bcr1271","article-title":"Estrogen-repressed genes\u2014key mediators of estrogen action","volume":"7","author":"Zubairy","year":"2005","journal-title":"Breast Cancer Res"},{"key":"2022071009460347200_CIT0026","doi-asserted-by":"crossref","first-page":"5858","DOI":"10.1128\/MCB.15.11.5858","article-title":"Widely spaced, directly repeated PuGGTCA elements act as promiscuous enhancers for different classes of nuclear receptors","volume":"15","author":"Kato","year":"1995","journal-title":"Mol. Cell. Biol"},{"key":"2022071009460347200_CIT0027","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/39645","article-title":"Molecular basis of agonism and antagonism in the oestrogen receptor","volume":"389","author":"Brzozowski","year":"1997","journal-title":"Nature"},{"key":"2022071009460347200_CIT0028","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0039-128X(99)00107-5","article-title":"Estrogen receptor interaction with co-activators and co-repressors","volume":"65","author":"Klinge","year":"2000","journal-title":"Steroids"},{"key":"2022071009460347200_CIT0029","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.1210\/en.2004-0308","article-title":"Thyroid hormone causes mitogen-activated protein kinase-dependent phosphorylation of the nuclear estrogen receptor","volume":"145","author":"Tang","year":"2004","journal-title":"Endocrinology"},{"key":"2022071009460347200_CIT0030","doi-asserted-by":"crossref","first-page":"21862","DOI":"10.1074\/jbc.M200764200","article-title":"Interaction of transcriptional intermediary factor 2 nuclear receptor box peptides with the coactivator binding site of estrogen receptor alpha","volume":"277","author":"W\u00e4rnmark","year":"2002","journal-title":"J. Biol. Chem"},{"key":"2022071009460347200_CIT0031","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1021\/cr400161b","article-title":"Retinoic acid actions through mammalian nuclear receptors","volume":"114","author":"Huang","year":"2014","journal-title":"Chem. Rev"},{"key":"2022071009460347200_CIT0032","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.biocel.2015.08.012","article-title":"Estrogen receptor signal in regulation of B cell activation during diverse immune responses","volume":"68","author":"Asaba","year":"2015","journal-title":"Int. J. Biochem. Cell Biol"},{"issue":"Pt 4","key":"2022071009460347200_CIT0033","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1242\/jcs.00247","article-title":"The nuclear receptor superfamily","volume":"116","author":"Robinson-Rechavi","year":"2003","journal-title":"J. Cell Sci"},{"key":"2022071009460347200_CIT0034","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/nchembio.1214","article-title":"Ligand-binding dynamics rewire cellular signaling via estrogen receptor-\u03b1","volume":"9","author":"Srinivasan","year":"2013","journal-title":"Nat. Chem. Biol"},{"issue":"2 Pt 1","key":"2022071009460347200_CIT0035","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/S0091-6749(99)70503-8","article-title":"Estrogen enhances immunoglobulin production by human PBMCs","volume":"103","author":"Kanda","year":"1999","journal-title":"J. Allergy Clin. Immunol"},{"key":"2022071009460347200_CIT0036","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1016\/j.vaccine.2011.01.080","article-title":"17\u03b2-Estradiol restores antibody responses to an influenza vaccine in a postmenopausal mouse model","volume":"29","author":"Nguyen","year":"2011","journal-title":"Vaccine"},{"key":"2022071009460347200_CIT0037","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/jaut.1993.1023","article-title":"Antibodies to cardiolipin in normal C57BL\/6J mice: induction by estrogen but not dihydrotestosterone","volume":"6","author":"Ahmed","year":"1993","journal-title":"J. Autoimmun"},{"key":"2022071009460347200_CIT0038","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1006\/jaut.1996.0121","article-title":"Characterization of estrogen-induced autoantibodies to cardiolipin in non-autoimmune mice","volume":"10","author":"Verthelyi","year":"1997","journal-title":"J. Autoimmun"},{"key":"2022071009460347200_CIT0039","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1093\/humrep\/deg292","article-title":"Association of serum complement (C3, C4) and immunoglobulin (IgG, IgM) levels with hormone replacement therapy in healthy post-menopausal women","volume":"18","author":"Yilmazer","year":"2003","journal-title":"Hum. Reprod"},{"key":"2022071009460347200_CIT0040","doi-asserted-by":"crossref","first-page":"6264","DOI":"10.1016\/j.vaccine.2017.09.069","article-title":"Prevnar-13 vaccine failure in a mouse model for vitamin A deficiency","volume":"35","author":"Penkert","year":"2017","journal-title":"Vaccine"},{"key":"2022071009460347200_CIT0041","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1128\/CVI.05576-11","article-title":"Reduced frequencies and heightened CD103 expression among virus-induced CD8(+) T cells in the respiratory tract airways of vitamin A-deficient mice","volume":"19","author":"Rudraraju","year":"2012","journal-title":"Clin. Vaccine Immunol"},{"key":"2022071009460347200_CIT0042","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1128\/CVI.00757-13","article-title":"Intranasal administration of retinyl palmitate with a respiratory virus vaccine corrects impaired mucosal IgA response in the vitamin A-deficient host","volume":"21","author":"Surman","year":"2014","journal-title":"Clin. Vaccine Immunol"},{"key":"2022071009460347200_CIT0043","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1016\/j.vaccine.2014.03.025","article-title":"Oral retinyl palmitate or retinoic acid corrects mucosal IgA responses toward an intranasal influenza virus vaccine in vitamin A deficient mice","volume":"32","author":"Surman","year":"2014","journal-title":"Vaccine"},{"key":"2022071009460347200_CIT0044","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1128\/CVI.00739-15","article-title":"Vitamin supplementation at the time of immunization with a cold-adapted influenza virus vaccine corrects poor mucosal antibody responses in mice deficient for vitamins A and D","volume":"23","author":"Surman","year":"2016","journal-title":"Clin. Vaccine Immunol"},{"key":"2022071009460347200_CIT0045","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1089\/vim.2012.0023","article-title":"Vitamin A deficiency disrupts vaccine-induced antibody-forming cells and the balance of IgA\/IgG isotypes in the upper and lower respiratory tract","volume":"25","author":"Surman","year":"2012","journal-title":"Viral Immunol"},{"key":"2022071009460347200_CIT0046","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nri2394","article-title":"The X-files in immunity: sex-based differences predispose immune responses","volume":"8","author":"Fish","year":"2008","journal-title":"Nat. Rev. Immunol"},{"key":"2022071009460347200_CIT0047","doi-asserted-by":"crossref","first-page":"j5560","DOI":"10.1136\/bmj.j5560","article-title":"The science behind \u201cman flu\u201d","volume":"359","author":"Sue","year":"2017","journal-title":"Br. J. Med"},{"key":"2022071009460347200_CIT0048","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1084\/jem.20080521","article-title":"Estrogen directly activates AID transcription and function","volume":"206","author":"Pauklin","year":"2009","journal-title":"J. Exp. Med"},{"key":"2022071009460347200_CIT0049","doi-asserted-by":"crossref","first-page":"37797","DOI":"10.1074\/jbc.M110.169086","article-title":"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","volume":"285","author":"Mai","year":"2010","journal-title":"J. Biol. Chem"},{"key":"2022071009460347200_CIT0050","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/ni.1725","article-title":"HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation","volume":"10","author":"Park","year":"2009","journal-title":"Nat. Immunol"},{"key":"2022071009460347200_CIT0051","doi-asserted-by":"crossref","first-page":"5370","DOI":"10.4049\/jimmunol.1401849","article-title":"IgH chain class switch recombination: mechanism and regulation","volume":"193","author":"Stavnezer","year":"2014","journal-title":"J. Immunol"},{"key":"2022071009460347200_CIT0052","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1038\/emboj.2011.56","article-title":"Sense transcription through the S region is essential for immunoglobulin class switch recombination","volume":"30","author":"Haddad","year":"2011","journal-title":"EMBO J"},{"key":"2022071009460347200_CIT0053","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/0014-5793(88)80111-X","article-title":"Thyroxine and testosterone transcriptionally regulate renin gene expression in the submaxillary gland of normal and transgenic mice carrying extra copies of the Ren2 gene","volume":"234","author":"Tronik","year":"1988","journal-title":"FEBS Lett"},{"key":"2022071009460347200_CIT0054","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.jsbmb.2008.06.009","article-title":"Estrogen and progesterone regulate the IL-6 signal transduction pathway in antibody secreting cells","volume":"111","author":"Canellada","year":"2008","journal-title":"J. Steroid Biochem. Mol. Biol"},{"key":"2022071009460347200_CIT0055","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S0021-9258(18)54192-2","article-title":"Multiple parameters control the selectivity of nuclear receptors for their response elements. Selectivity and promiscuity in response element recognition by retinoic acid receptors and retinoid X receptors","volume":"268","author":"Mader","year":"1993","journal-title":"J. Biol. Chem"},{"key":"2022071009460347200_CIT0056","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1023\/A:1006841230054","article-title":"The 3-flanking region of the mouse c-fos gene contains a cluster of GGTCA hormone response-like elements","volume":"25","author":"Hyder","year":"1998","journal-title":"Mol. Biol. Rep"},{"key":"2022071009460347200_CIT0057","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1210\/me.2011-1311","article-title":"Research resource: whole-genome estrogen receptor \u03b1 binding in mouse uterine tissue revealed by ChIP-seq","volume":"26","author":"Hewitt","year":"2012","journal-title":"Mol. Endocrinol"},{"key":"2022071009460347200_CIT0058","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1210\/me.2014-1051","article-title":"Novel DNA motif binding activity observed in vivo with an estrogen receptor \u03b1 mutant mouse","volume":"28","author":"Hewitt","year":"2014","journal-title":"Mol. Endocrinol"},{"key":"2022071009460347200_CIT0059","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4049\/jimmunol.161.1.27","article-title":"The role of estrogen receptors and androgen receptors in sex steroid regulation of B lymphopoiesis","volume":"161","author":"Smithson","year":"1998","journal-title":"J. Immunol"},{"key":"2022071009460347200_CIT0060","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.clim.2008.03.508","article-title":"Impact of estrogen receptor deficiency on disease expression in the NZM2410 lupus prone mouse","volume":"128","author":"Svenson","year":"2008","journal-title":"Clin. Immunol"},{"key":"2022071009460347200_CIT0061","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/ilar.45.4.455","article-title":"Estrogen receptor knockout mice as a model for endocrine research","volume":"45","author":"Walker","year":"2004","journal-title":"ILAR J"},{"key":"2022071009460347200_CIT0062","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1128\/JVI.78.2.995-998.2004","article-title":"Imparting temperature sensitivity and attenuation in ferrets to A\/Puerto Rico\/8\/34 influenza virus by transferring the genetic signature for temperature sensitivity from cold-adapted A\/Ann Arbor\/6\/60","volume":"78","author":"Jin","year":"2004","journal-title":"J. Virol"},{"key":"2022071009460347200_CIT0063","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.vaccine.2008.12.023","article-title":"A multi-valent vaccine approach that elicits broad immunity within an influenza subtype","volume":"27","author":"Huber","year":"2009","journal-title":"Vaccine"},{"key":"2022071009460347200_CIT0064","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1126\/science.1218692","article-title":"AID-driven deletion causes immunoglobulin heavy chain locus suicide recombination in B cells","volume":"336","author":"P\u00e9ron","year":"2012","journal-title":"Science"},{"key":"2022071009460347200_CIT0065","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1084\/jem.20082311","article-title":"Ikaros controls isotype selection during immunoglobulin class switch recombination","volume":"206","author":"Sellars","year":"2009","journal-title":"J. Exp. Med"},{"key":"2022071009460347200_CIT0066","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2022071009460347200_CIT0067","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.exger.2006.09.003","article-title":"Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF","volume":"42","author":"Frasca","year":"2007","journal-title":"Exp. Gerontol"},{"key":"2022071009460347200_CIT0068","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.arr.2010.08.004","article-title":"Age effects on B cells and humoral immunity in humans","volume":"10","author":"Frasca","year":"2011","journal-title":"Ageing Res. Rev"},{"key":"2022071009460347200_CIT0069","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1089\/vim.2015.0104","article-title":"Hotspots for vitamin-steroid-thyroid hormone response elements within switch regions of immunoglobulin heavy chain loci predict a direct influence of vitamins and hormones on B cell class switch recombination","volume":"29","author":"Hurwitz","year":"2016","journal-title":"Viral Immunol"},{"key":"2022071009460347200_CIT0070","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.molimm.2016.07.015","article-title":"Binding of estrogen receptors to switch sites and regulatory elements in the immunoglobulin heavy chain locus of activated B cells suggests a direct influence of estrogen on antibody expression","volume":"77","author":"Jones","year":"2016","journal-title":"Mol. Immunol"},{"key":"2022071009460347200_CIT0071","doi-asserted-by":"crossref","first-page":"7041","DOI":"10.1073\/pnas.81.22.7041","article-title":"Two regulatory elements for immunoglobulin kappa light chain gene expression","volume":"81","author":"Bergman","year":"1984","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2022071009460347200_CIT0072","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/0092-8674(95)90138-8","article-title":"The 3\u2019 enhancer region determines the B\/T specificity and pro-B\/pre-B specificity of immunoglobulin V kappa-J kappa joining","volume":"83","author":"Hiramatsu","year":"1995","journal-title":"Cell"},{"key":"2022071009460347200_CIT0073","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1007\/s00251-004-0659-0","article-title":"Assembly and analysis of the mouse immunoglobulin kappa gene sequence","volume":"56","author":"Brekke","year":"2004","journal-title":"Immunogenetics"},{"key":"2022071009460347200_CIT0074","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.4049\/jimmunol.1203127","article-title":"V\u03ba gene repertoire and locus contraction are specified by critical DNase I hypersensitive sites within the V\u03ba-J\u03ba intervening region","volume":"190","author":"Xiang","year":"2013","journal-title":"J. Immunol"},{"key":"2022071009460347200_CIT0075","first-page":"2619","article-title":"The immunoglobulin heavy-chain enhancer functions as the promoter for I mu sterile transcription","volume":"10","author":"Su","year":"1990","journal-title":"Mol. Cell. Biol"},{"key":"2022071009460347200_CIT0076","doi-asserted-by":"crossref","first-page":"14362","DOI":"10.1073\/pnas.0507090102","article-title":"Elucidation of IgH intronic enhancer functions via germ-line deletion","volume":"102","author":"Perlot","year":"2005","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2022071009460347200_CIT0077","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.cell.2011.08.049","article-title":"Two forms of loops generate the chromatin conformation of the immunoglobulin heavy-chain gene locus","volume":"147","author":"Guo","year":"2011","journal-title":"Cell"},{"key":"2022071009460347200_CIT0078","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1084\/jem.20141967","article-title":"Mediator facilitates transcriptional activation and dynamic long-range contacts at the IgH locus during class switch recombination","volume":"213","author":"Thomas-Claudepierre","year":"2016","journal-title":"J. Exp. Med"},{"key":"2022071009460347200_CIT0079","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.smim.2012.06.001","article-title":"AID targeting is dependent on RNA polymerase II pausing","volume":"24","author":"Kenter","year":"2012","journal-title":"Semin. Immunol"},{"key":"2022071009460347200_CIT0080","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fimmu.2014.00163","article-title":"Epigenetic regulation of individual modules of the immunoglobulin heavy chain locus 3\u2019 regulatory region","volume":"5","author":"Birshtein","year":"2014","journal-title":"Front. Immunol"},{"key":"2022071009460347200_CIT0081","doi-asserted-by":"crossref","first-page":"29303","DOI":"10.1074\/jbc.M111.243543","article-title":"Dynamic changes in binding of immunoglobulin heavy chain 3\u2019 regulatory region to protein factors during class switching","volume":"286","author":"Chatterjee","year":"2011","journal-title":"J. Biol. Chem"},{"key":"2022071009460347200_CIT0082","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1084\/jem.186.6.845","article-title":"Enhancer complexes located downstream of both human immunoglobulin Calpha genes","volume":"186","author":"Mills","year":"1997","journal-title":"J. Exp. Med"},{"key":"2022071009460347200_CIT0083","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.molimm.2011.08.024","article-title":"Interaction between the immunoglobulin heavy chain 3\u2019 regulatory region and the IgH transcription unit during B cell differentiation","volume":"49","author":"Ju","year":"2011","journal-title":"Mol. Immunol"},{"key":"2022071009460347200_CIT0084","doi-asserted-by":"crossref","first-page":"13693","DOI":"10.1073\/pnas.212392399","article-title":"The origin of a developmentally regulated Igh replicon is located near the border of regulatory domains for Igh replication and expression","volume":"99","author":"Zhou","year":"2002","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2022071009460347200_CIT0085","doi-asserted-by":"crossref","first-page":"127","DOI":"10.4161\/trns.24556","article-title":"Transcriptional stalling in B-lymphocytes: a mechanism for antibody diversification and maintenance of genomic integrity","volume":"4","author":"Sun","year":"2013","journal-title":"Transcription"},{"key":"2022071009460347200_CIT0086","doi-asserted-by":"crossref","first-page":"6380","DOI":"10.4049\/jimmunol.164.12.6380","article-title":"Regulation of germline promoters by the two human Ig heavy chain 3\u2019 alpha enhancers","volume":"164","author":"Hu","year":"2000","journal-title":"J. Immunol"},{"key":"2022071009460347200_CIT0087","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.gene.2004.10.009","article-title":"Evolution of human IgH3\u2019EC duplicated structures: both enhancers HS1,2 are polymorphic with variation of transcription factor\u2019s consensus sites","volume":"346","author":"Giambra","year":"2005","journal-title":"Gene"},{"key":"2022071009460347200_CIT0088","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1136\/ard.2010.147025","article-title":"Polymorphisms of the IgH enhancer HS1.2 and risk of systemic lupus erythematosus","volume":"71","author":"Frezza","year":"2012","journal-title":"Ann. Rheum. Dis"},{"key":"2022071009460347200_CIT0089","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.gene.2014.08.057","article-title":"The functional VNTR of IGH enhancer HS1.2 associates with human longevity and interacts with TNFA promoter diplotype in a population of Central Italy","volume":"551","author":"Napolioni","year":"2014","journal-title":"Gene"},{"key":"2022071009460347200_CIT0090","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0192-0561(99)00090-9","article-title":"Strain differences in binding properties of estrogen receptors in immature and adult BALB\/c and MRL\/MP-lpr\/lpr mice, a model of systemic lupus erythematosus","volume":"22","author":"Dhaher","year":"2000","journal-title":"Int. J. Immunopharmacol"},{"issue":"12 Pt 1","key":"2022071009460347200_CIT0091","doi-asserted-by":"crossref","first-page":"953","DOI":"10.7326\/0003-4819-142-12_Part_1-200506210-00004","article-title":"The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial","volume":"142","author":"Buyon","year":"2005","journal-title":"Ann. Intern. Med"},{"key":"2022071009460347200_CIT0092","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1196\/annals.1386.043","article-title":"Estrogens and autoimmune diseases","volume":"1089","author":"Cutolo","year":"2006","journal-title":"Ann. NY Acad. Sci"},{"key":"2022071009460347200_CIT0093","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/ni0901-777","article-title":"Sex differences in autoimmune disease","volume":"2","author":"Whitacre","year":"2001","journal-title":"Nat. Immunol"},{"key":"2022071009460347200_CIT0094","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1177\/0961203306069353","article-title":"Sex differences in autoimmune disease","volume":"15","author":"Lockshin","year":"2006","journal-title":"Lupus"},{"key":"2022071009460347200_CIT0095","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/0896-8411(89)90013-9","article-title":"Serum concentrations of IgM, IgG1, IgG2b, IgG3 and IgA in C57BL\/6 mice and their congenics at the lpr (lymphoproliferation) locus","volume":"2","author":"Klein-Schneegans","year":"1989","journal-title":"J. Autoimmun"},{"key":"2022071009460347200_CIT0096","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1080\/00365520410007999","article-title":"Increased frequency of the immunoglobulin enhancer HS1,2 allele 2 in coeliac disease","volume":"39","author":"Frezza","year":"2004","journal-title":"Scand. J. Gastroenterol"},{"key":"2022071009460347200_CIT0097","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1038\/jid.2008.40","article-title":"Increased frequency of Ig heavy-chain HS1,2-A enhancer *2 allele in dermatitis herpetiformis, plaque psoriasis, and psoriatic arthritis","volume":"128","author":"Cianci","year":"2008","journal-title":"J. Invest. Dermatol"},{"key":"2022071009460347200_CIT0098","first-page":"3618","article-title":"The involvement of IgH enhancer HS1.2 in the pathogenesis of Crohn\u2019s disease: how the immune system can influence a multifactorial disease","volume":"20","author":"Cianci","year":"2016","journal-title":"Eur. Rev. Med. Pharmacol. Sci"},{"issue":"Pt 6","key":"2022071009460347200_CIT0099","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1111\/j.1469-1809.2006.00273.x","article-title":"Immunoglobulin enhancer HS1,2 polymorphism: a new powerful anthropogenetic marker","volume":"70","author":"Giambra","year":"2006","journal-title":"Ann. Hum. Genet"},{"key":"2022071009460347200_CIT0100","doi-asserted-by":"crossref","first-page":"8280","DOI":"10.4049\/jimmunol.0902426","article-title":"Allele *1 of HS1.2 enhancer associates with selective IgA deficiency and IgM concentration","volume":"183","author":"Giambra","year":"2009","journal-title":"J. Immunol"},{"key":"2022071009460347200_CIT0101","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/art.1780160215","article-title":"Influence of natural and synthetic estrogens on the course of autoimmune disease in the NZB-NZW mouse","volume":"16","author":"Walker","year":"1973","journal-title":"Arthritis Rheum"},{"key":"2022071009460347200_CIT0102","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/art.1780150107","article-title":"Distinctive serum globulin responses to parenteral treatment with 17-beta-estradiol in female NZB\/NZW mice","volume":"15","author":"Walker","year":"1972","journal-title":"Arthritis Rheum"},{"key":"2022071009460347200_CIT0103","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1136\/pgmj.57.673.714","article-title":"Reversible IgA deficiency in hypothyroidism","volume":"57","author":"Eriksson","year":"1981","journal-title":"Postgrad. Med. J"},{"key":"2022071009460347200_CIT0104","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.2169\/internalmedicine.31.1201","article-title":"Isolated IgA deficiency accompanied by autoimmune thyroid disease","volume":"31","author":"Mano","year":"1992","journal-title":"Intern. Med"},{"key":"2022071009460347200_CIT0105","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1046\/j.1523-1747.2003.12493.x","article-title":"Inhibition of IgE-production by peroxisome proliferator-activated receptor ligands","volume":"121","author":"R\u00fchl","year":"2003","journal-title":"J. Invest. Dermatol"},{"key":"2022071009460347200_CIT0106","doi-asserted-by":"crossref","first-page":"6903","DOI":"10.4049\/jimmunol.0900324","article-title":"Peroxisome proliferator-activated receptor gamma ligands enhance human B cell antibody production and differentiation","volume":"183","author":"Garcia-Bates","year":"2009","journal-title":"J. Immunol"},{"key":"2022071009460347200_CIT0107","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/192565a0","article-title":"Effect of diethylstilboestrol on the serum gamma-globulin in the guinea pig","volume":"192","author":"Charles","year":"1961","journal-title":"Nature"},{"key":"2022071009460347200_CIT0108","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1128\/iai.13.2.448-456.1976","article-title":"Effect of estradiol on immune competence: in vivo and in vitro studies","volume":"13","author":"Kenny","year":"1976","journal-title":"Infect. Immun"},{"key":"2022071009460347200_CIT0109","doi-asserted-by":"crossref","first-page":"e55842","DOI":"10.1371\/journal.pone.0055842","article-title":"Transgenes of the mouse immunoglobulin heavy chain locus, lacking distal elements in the 3\u2019 regulatory region, are impaired for class switch recombination","volume":"8","author":"Dunnick","year":"2013","journal-title":"PLoS One"},{"key":"2022071009460347200_CIT0110","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1073\/pnas.1514090113","article-title":"Sequential activation and distinct functions for distal and proximal modules within the IgH 3\u2019 regulatory region","volume":"113","author":"Garot","year":"2016","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2022071009460347200_CIT0111","doi-asserted-by":"crossref","first-page":"4780","DOI":"10.4049\/jimmunol.158.10.4780","article-title":"Dyad symmetry within the mouse 3\u2019 IgH regulatory region includes two virtually identical enhancers (C alpha3\u2019E and hs3)","volume":"158","author":"Saleque","year":"1997","journal-title":"J. Immunol"},{"key":"2022071009460347200_CIT0112","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.4049\/jimmunol.1102763","article-title":"Germline deletion of Igh 3\u2019 regulatory region elements hs 5, 6, 7 (hs5-7) affects B cell-specific regulation, rearrangement, and insulation of the Igh locus","volume":"188","author":"Volpi","year":"2012","journal-title":"J. Immunol"},{"key":"2022071009460347200_CIT0113","doi-asserted-by":"crossref","first-page":"4876","DOI":"10.1128\/MCB.22.13.4876-4889.2002","article-title":"Replication and subnuclear location dynamics of the immunoglobulin heavy-chain locus in B-lineage cells","volume":"22","author":"Zhou","year":"2002","journal-title":"Mol. Cell. Biol"},{"key":"2022071009460347200_CIT0114","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/ni.1964","article-title":"Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes","volume":"12","author":"Yamane","year":"2011","journal-title":"Nat. Immunol"},{"key":"2022071009460347200_CIT0115","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1084\/jem.20130166","article-title":"The cohesin complex regulates immunoglobulin class switch recombination","volume":"210","author":"Thomas-Claudepierre","year":"2013","journal-title":"J. Exp. Med"},{"key":"2022071009460347200_CIT0116","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature13992","article-title":"A comparative encyclopedia of DNA elements in the mouse genome","volume":"515","author":"Yue","year":"2014","journal-title":"Nature"},{"key":"2022071009460347200_CIT0117","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.4049\/jimmunol.167.6.3257","article-title":"HS1,2 enhancer regulation of germline epsilon and gamma2b promoters in murine B lymphocytes: evidence for specific promoter-enhancer interactions","volume":"167","author":"Laurencikiene","year":"2001","journal-title":"J. Immunol"},{"key":"2022071009460347200_CIT0118","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/ni.3249","article-title":"Histone reader BRWD1 targets and restricts recombination to the Igk locus","volume":"16","author":"Mandal","year":"2015","journal-title":"Nat. Immunol"},{"key":"2022071009460347200_CIT0119","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.rdc.2007.01.002","article-title":"Lupus activity in pregnancy","volume":"33","author":"Clowse","year":"2007","journal-title":"Rheum. Dis. Clin. North Am"},{"key":"2022071009460347200_CIT0120","first-page":"67","article-title":"Sex hormones and SLE: influencing the fate of autoreactive B cells","volume":"305","author":"Cohen-Solal","year":"2006","journal-title":"Curr. Top. Microbiol. Immunol"},{"key":"2022071009460347200_CIT0121","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.autrev.2017.02.001","article-title":"Lupus nephritis and pregnancy outcome","volume":"16","author":"Schreiber","year":"2017","journal-title":"Autoimmun. Rev"},{"key":"2022071009460347200_CIT0122","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1073\/pnas.0307915100","article-title":"Autoimmune glomerulonephritis with spontaneous formation of splenic germinal centers in mice lacking the estrogen receptor alpha gene","volume":"101","author":"Shim","year":"2004","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["International Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/31\/3\/141\/44799278\/dxy074.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/31\/3\/141\/44799278\/dxy074.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T18:37:44Z","timestamp":1694025464000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/intimm\/article\/31\/3\/141\/5164357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,8]]},"references-count":122,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,11,8]]},"published-print":{"date-parts":[[2019,3,5]]}},"URL":"https:\/\/doi.org\/10.1093\/intimm\/dxy074","relation":{},"ISSN":["1460-2377"],"issn-type":[{"value":"1460-2377","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,3]]},"published":{"date-parts":[[2018,11,8]]}}}