{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:18:44Z","timestamp":1789525124582,"version":"build-2803163510"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hypoxia has been shown to shape the humoral immune response within germinal centers, where B cells diversify their receptors through somatic hypermutation (SHM) and class switch recombination (CSR). Both processes are initiated by activation\u2010induced cytidine deaminase (AID), which deaminates cytosines into uracils in immunoglobulin genes, leading to point mutations during SHM or to double\u2010stranded DNA breaks during CSR. Although AID's function is well characterized, the mechanisms governing its expression remain ill\u2010defined. We previously identified the hypoxia\u2010inducible transcription factor (HIF) transcription complex (comprised of HIF\u20101\u03b1, HIF\u20101\u03b2, and the auxiliary subunits HIF\u20102\u03b1 and HIF\u20103\u03b1) as a regulator of optimal AID expression during CSR. Indeed, loss of HIF\u20101\u03b1 or HIF\u20101\u03b2 delays AID expression and impairs CSR. Here, we examine the contribution of HIF\u20102\u03b1 and HIF\u20103\u03b1. We show that deficiency in HIF\u20102\u03b1, but not HIF\u20103\u03b1, impairs CSR, whereas combined loss of HIF\u20101\u03b1 and HIF\u20102\u03b1 does not exacerbate the defect, indicating that HIF\u20101\u03b1 is the dominant subunit driving this process. Importantly, we demonstrate that hypoxia can induce AID expression, independently of additional stimuli. Collectively, these findings reveal that hypoxia regulates AID expression in a context\u2010 and time\u2010dependent manner through HIF activation. This underscores the central role of hypoxic signaling in antibody diversification and suggests broader implications for immune regulation and the onset of B\u2010cell malignancies.<\/jats:p>","DOI":"10.1002\/eji.70208","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:34:47Z","timestamp":1779194087000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hypoxia Independently Induces AID Expression in CH12 B Cells"],"prefix":"10.1002","volume":"56","author":[{"given":"Vincent","family":"Heyer","sequence":"first","affiliation":[{"name":"Institut De G\u00e9n\u00e9tique et De Biologie Mol\u00e9culaire Et Cellulaire (IGBMC)  Illkirch France"},{"name":"Institut National de La Sant\u00e9 et De La Recherche M\u00e9dicale (INSERM)  Illkirch France"},{"name":"Centre National de La Recherche Scientifique (CNRS)  Illkirch France"},{"name":"Universit\u00e9 De Strasbourg  Illkirch France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy","family":"Haidar Ahmad","sequence":"additional","affiliation":[{"name":"Institut De G\u00e9n\u00e9tique et De Biologie Mol\u00e9culaire Et Cellulaire (IGBMC)  Illkirch France"},{"name":"Institut National de La Sant\u00e9 et De La Recherche M\u00e9dicale (INSERM)  Illkirch France"},{"name":"Centre National de La Recherche Scientifique (CNRS)  Illkirch France"},{"name":"Universit\u00e9 De Strasbourg  Illkirch France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Haddad","sequence":"additional","affiliation":[{"name":"Institut De G\u00e9n\u00e9tique et De Biologie Mol\u00e9culaire Et Cellulaire (IGBMC)  Illkirch France"},{"name":"Institut National de La Sant\u00e9 et De La Recherche M\u00e9dicale (INSERM)  Illkirch France"},{"name":"Centre National de La Recherche Scientifique (CNRS)  Illkirch France"},{"name":"Universit\u00e9 De Strasbourg  Illkirch France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e8s","family":"Argentieri","sequence":"additional","affiliation":[{"name":"Institut De G\u00e9n\u00e9tique et De Biologie Mol\u00e9culaire Et Cellulaire (IGBMC)  Illkirch France"},{"name":"Institut National de La Sant\u00e9 et De La Recherche M\u00e9dicale (INSERM)  Illkirch France"},{"name":"Centre National de La Recherche Scientifique (CNRS)  Illkirch France"},{"name":"Universit\u00e9 De Strasbourg  Illkirch France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coraline","family":"Gessier","sequence":"additional","affiliation":[{"name":"Institut De G\u00e9n\u00e9tique et De Biologie Mol\u00e9culaire Et Cellulaire (IGBMC)  Illkirch France"},{"name":"Institut National de La Sant\u00e9 et De La Recherche M\u00e9dicale (INSERM)  Illkirch France"},{"name":"Centre National de La Recherche Scientifique (CNRS)  Illkirch France"},{"name":"Universit\u00e9 De Strasbourg  Illkirch France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo","family":"Reina\u2010San\u2010Martin","sequence":"additional","affiliation":[{"name":"Institut De G\u00e9n\u00e9tique et De Biologie Mol\u00e9culaire Et Cellulaire (IGBMC)  Illkirch France"},{"name":"Institut National de La Sant\u00e9 et De La Recherche M\u00e9dicale (INSERM)  Illkirch France"},{"name":"Centre National de La Recherche Scientifique (CNRS)  Illkirch France"},{"name":"Universit\u00e9 De Strasbourg  Illkirch 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