{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:35:05Z","timestamp":1787009705065,"version":"build-2736575974"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["NIEHS R01ES014676"],"award-info":[{"award-number":["NIEHS R01ES014676"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Pharmacology & Toxicology, Boonshoft School of Medicine"},{"DOI":"10.13039\/100010288","name":"Wright State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010288","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant and high affinity ligand for the aryl hydrocarbon receptor (AhR). In animal models, AhR activation by TCDD generally inhibits antibody secretion. However, it is less clear if this translates to human antibody production. Using a human Burkitt lymphoma B-cell line (CL-01) that can be stimulated to secrete Ig and undergo class switch recombination to other Ig isotypes, the current study evaluated the effects of AhR activation or antagonism on the human Ig isotypic expression profile with CD40L+IL-4 stimulation. Our results suggest that AhR agonists (TCDD and indirubin) have little to no effect on IgM or IgA secretion, which were also not induced with stimulation. However, AhR activation significantly inhibited stimulation-induced IgG secretion, an effect reversed by the AhR antagonist CH223191. Evaluation of Ig heavy chain (IgH) constant region gene expression (ie C\u03bc, C\u03b31-4, C\u03b11-2, and C\u03b5 that encode for IgM, IgG1-4, IgA1-2, and IgE, respectively) demonstrated differential effects. While C\u03bc and C\u03b12 transcripts were unaffected by stimulation or AhR agonists, AhR activation significantly inhibited stimulation-induced C\u03b32-4 and C\u03b5 mRNA transcripts, which was reversed by AhR antagonism. Notably, AhR antagonism in the absence of exogenous AhR ligands significantly increased IgG and IgA secretion as well as the expression of C\u03b32-4 and C\u03b5. These results suggest that modulation of AhR activity differentially alters the IgH isotypic expression profile and antibody secretion that may be partly dependent on cellular stimulation. Since a variety of chemicals from anthropogenic, industrial, pharmaceutical, dietary, and bacterial sources bind the AhR, the ability of environmental exposures to alter AhR activity (i.e. activate or inhibit) may have a direct influence on immune function and antibody-relevant disease conditions.<\/jats:p>","DOI":"10.1093\/toxsci\/kfae035","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T03:56:39Z","timestamp":1711079799000},"page":"276-288","source":"Crossref","is-referenced-by-count":6,"title":["The aryl hydrocarbon receptor differentially modulates the expression profile of antibody isotypes in a human B-cell line"],"prefix":"10.1093","volume":"199","author":[{"given":"Mili S","family":"Bhakta-Yadav","sequence":"first","affiliation":[{"name":"Department of Pharmacology & Toxicology, Boonshoft School of Medicine, Wright State University , Dayton, Ohio 45435, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaulini","family":"Burra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Boonshoft School of Medicine, Wright State University , Dayton, Ohio 45435, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasser","family":"Alhamdan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Boonshoft School of Medicine, Wright State University , Dayton, Ohio 45435, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton P","family":"Allex-Buckner","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Boonshoft School of Medicine, Wright State University , Dayton, Ohio 45435, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1160-8217","authenticated-orcid":false,"given":"Courtney E W","family":"Sulentic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Boonshoft School of Medicine, Wright State University , Dayton, Ohio 45435, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"2024052809254327400_kfae035-B1","doi-asserted-by":"crossref","first-page":"31475","DOI":"10.1074\/jbc.C100238200","article-title":"Indirubin and indigo are potent aryl hydrocarbon receptor ligands present in human urine","volume":"276","author":"Adachi","year":"2001","journal-title":"J. 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