{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:30:10Z","timestamp":1791523810181,"version":"4.3.4"},"reference-count":76,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"34","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,8,26]]},"abstract":"<jats:p>\n            Immunoglobulin class switch recombination (CSR) plays critical roles in controlling infections and inflammatory tissue injuries. Here, we show that\n            <jats:italic>AFF3<\/jats:italic>\n            , a candidate gene for both rheumatoid arthritis and type 1 diabetes, is a molecular facilitator of CSR with an isotype preference.\n            <jats:italic>Aff3<\/jats:italic>\n            -deficient mice exhibit low serum levels of immunoglobulins, predominantly immunoglobulin G2c (IgG2c) followed by IgG1 and IgG3 but not IgM. Furthermore,\n            <jats:italic>Aff3<\/jats:italic>\n            -deficient mice show weak resistance to\n            <jats:italic>Plasmodium yoelii<\/jats:italic>\n            infection, confirming that\n            <jats:italic>Aff3<\/jats:italic>\n            modulates immunity to this pathogen. Mechanistically, the AFF3 protein binds to the IgM and IgG1 switch regions via a C-terminal domain, and\n            <jats:italic>Aff3<\/jats:italic>\n            deficiency reduces the binding of AID to the switch regions less efficiently. One\n            <jats:italic>AFF3<\/jats:italic>\n            risk allele for rheumatoid arthritis is associated with high mRNA expression of\n            <jats:italic>AFF3<\/jats:italic>\n            ,\n            <jats:italic>IGHG2<\/jats:italic>\n            , and\n            <jats:italic>IGHA2<\/jats:italic>\n            in human B cells. These findings demonstrate that AFF3 directly regulates CSR by facilitating the recruitment of AID to the switch regions.\n          <\/jats:p>","DOI":"10.1126\/sciadv.abq0008","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T17:57:32Z","timestamp":1661363852000},"source":"Crossref","is-referenced-by-count":28,"title":["AFF3, a susceptibility factor for autoimmune diseases, is a molecular facilitator of immunoglobulin class switch recombination"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7950-3900","authenticated-orcid":true,"given":"Shin-ichi","family":"Tsukumo","sequence":"first","affiliation":[{"name":"Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan."},{"name":"Department of Interdisciplinary Research on Medicine and Photonics, Institute of Post-LED Photonics, Tokushima University, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7318-6577","authenticated-orcid":true,"given":"Poorani Ganesh","family":"Subramani","sequence":"additional","affiliation":[{"name":"Institut de Recherches Cliniques de Montr\u00e9al, Montr\u00e9al, QC, Canada."},{"name":"Department of Medicine and Division of Experimental Medicine, McGill University, Montr\u00e9al, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2223-1291","authenticated-orcid":true,"given":"No\u00e9","family":"Seija","sequence":"additional","affiliation":[{"name":"Institut de Recherches Cliniques de Montr\u00e9al, Montr\u00e9al, QC, Canada."},{"name":"Molecular Biology Programs, Department of Medicine, University of Montreal, Montr\u00e9al, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuho","family":"Tabata","sequence":"additional","affiliation":[{"name":"Department of Parasitology and Infectious Diseases, Gifu University Graduate School of Medicine, Gifu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Maekawa","sequence":"additional","affiliation":[{"name":"Department of Parasitology and Infectious Diseases, Gifu University Graduate School of Medicine, Gifu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Mori","sequence":"additional","affiliation":[{"name":"Division of Pathogenesis and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Shiga, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieko","family":"Ishifune","sequence":"additional","affiliation":[{"name":"Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Itoh","sequence":"additional","affiliation":[{"name":"Division of Pathogenesis and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Shiga, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4552-8573","authenticated-orcid":true,"given":"Mineto","family":"Ota","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan."},{"name":"Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7276-5254","authenticated-orcid":true,"given":"Keishi","family":"Fujio","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2896-0321","authenticated-orcid":true,"given":"Javier M.","family":"Di Noia","sequence":"additional","affiliation":[{"name":"Institut de Recherches Cliniques de Montr\u00e9al, Montr\u00e9al, QC, Canada."},{"name":"Department of Medicine and Division of Experimental Medicine, McGill University, Montr\u00e9al, QC, Canada."},{"name":"Molecular Biology Programs, Department of Medicine, University of Montreal, Montr\u00e9al, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0411-2037","authenticated-orcid":true,"given":"Koji","family":"Yasutomo","sequence":"additional","affiliation":[{"name":"Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan."},{"name":"Department of Interdisciplinary Research on Medicine and Photonics, Institute of Post-LED Photonics, Tokushima University, Tokushima, Japan."},{"name":"The Research Cluster Program on Immunological Diseases, Tokushima University, Tokushima, 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