ID | 117850 |
Author |
Tsukumo, Shin-ichi
Tokushima University
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Subramani, Poorani Ganesh
Institut de Recherches Cliniques de Montréal|McGill University
Seija, Noé
Institut de Recherches Cliniques de Montréal|University of Montreal
Tabata, Mizuho
Gifu University
Maekawa, Yoichi
Gifu University
Mori, Yuya
Shiga University of Medical Science
Ishifune, Chieko
Tokushima University
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Itoh, Yasushi
Shiga University of Medical Science
Ota, Mineto
The University of Tokyo
Fujio, Keishi
The University of Tokyo
Di Noia, Javier M.
Institut de Recherches Cliniques de Montréal|McGill University|University of Montreal
Yasutomo, Koji
Tokushima University
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Content Type |
Journal Article
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Description | Immunoglobulin class switch recombination (CSR) plays critical roles in controlling infections and inflammatory tissue injuries. Here, we show that AFF3, a candidate gene for both rheumatoid arthritis and type 1 diabetes, is a molecular facilitator of CSR with an isotype preference. Aff3-deficient mice exhibit low serum levels of immunoglobulins, predominantly immunoglobulin G2c (IgG2c) followed by IgG1 and IgG3 but not IgM. Furthermore, Aff3-deficient mice show weak resistance to Plasmodium yoelii infection, confirming that Aff3 modulates immunity to this pathogen. Mechanistically, the AFF3 protein binds to the IgM and IgG1 switch regions via a C-terminal domain, and Aff3 deficiency reduces the binding of AID to the switch regions less efficiently. One AFF3 risk allele for rheumatoid arthritis is associated with high mRNA expression of AFF3, IGHG2, and IGHA2 in human B cells. These findings demonstrate that AFF3 directly regulates CSR by facilitating the recruitment of AID to the switch regions.
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Journal Title |
Science Advances
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ISSN | 23752548
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Publisher | American Association for the Advancement of Science
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Volume | 8
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Issue | 34
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Start Page | eabq0008
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Published Date | 2022-08-24
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Rights | © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC) (https://creativecommons.org/licenses/by-nc/4.0/).
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DOI (Published Version) | |
URL ( Publisher's Version ) | |
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language |
eng
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TextVersion |
Publisher
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departments |
Medical Sciences
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