A Germinal Center Checkpoint of AIRE in B Cells Limits Antibody Diversification
In response to antigens, B cells undergo affinity maturation and class switching mediated by activation-induced cytidine deaminase (AID) in germinal centers (GCs) of secondary lymphoid organs, but uncontrolled AID activity can precipitate autoimmunity and cancer. The regulation of GC antibody diversification is of fundamental importance but not well understood. We found that autoimmune regulator (AIRE), the molecule essential for T cell tolerance, is expressed in GC B cells in a CD40-dependent manner, interacts with AID and negatively regulates antibody affinity maturation and class switching by inhibiting AID function. AIRE deficiency in B cells caused altered antibody repertoire, increased somatic hypermutations, elevated autoantibodies to T helper 17 effector cytokines and defective control of skin Candida albicans. These results define a GC B cell checkpoint of humoral immunity and illuminate new approaches of generating high-affinity neutralizing antibodies for immunotherapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2024) vom: 12. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Jordan Z [VerfasserIn] |
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| Links: |
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| Themen: |
AID |
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| Anmerkungen: |
Date Revised 05.02.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2024.01.10.574926 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM36750846X |
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| 100 | 1 | |a Zhou, Jordan Z |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A Germinal Center Checkpoint of AIRE in B Cells Limits Antibody Diversification |
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| 500 | |a Date Revised 05.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a In response to antigens, B cells undergo affinity maturation and class switching mediated by activation-induced cytidine deaminase (AID) in germinal centers (GCs) of secondary lymphoid organs, but uncontrolled AID activity can precipitate autoimmunity and cancer. The regulation of GC antibody diversification is of fundamental importance but not well understood. We found that autoimmune regulator (AIRE), the molecule essential for T cell tolerance, is expressed in GC B cells in a CD40-dependent manner, interacts with AID and negatively regulates antibody affinity maturation and class switching by inhibiting AID function. AIRE deficiency in B cells caused altered antibody repertoire, increased somatic hypermutations, elevated autoantibodies to T helper 17 effector cytokines and defective control of skin Candida albicans. These results define a GC B cell checkpoint of humoral immunity and illuminate new approaches of generating high-affinity neutralizing antibodies for immunotherapy | ||
| 650 | 4 | |a Preprint | |
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| 650 | 4 | |a Humoral immunity | |
| 650 | 4 | |a antibody diversification | |
| 650 | 4 | |a autoimmunity | |
| 650 | 4 | |a checkpoint | |
| 650 | 4 | |a germinal center | |
| 650 | 4 | |a immunodeficiency | |
| 650 | 4 | |a immunotherapy | |
| 700 | 1 | |a Huang, Bihui |e verfasserin |4 aut | |
| 700 | 1 | |a Pei, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Guang Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Pawlitz, Michael D |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xinyang |e verfasserin |4 aut | |
| 700 | 1 | |a Hokynar, Kati C |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Fayi |e verfasserin |4 aut | |
| 700 | 1 | |a Perera, Madusha L W |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Shanqiao |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Simin |e verfasserin |4 aut | |
| 700 | 1 | |a Polin, Lisa A |e verfasserin |4 aut | |
| 700 | 1 | |a Poulik, Janet M |e verfasserin |4 aut | |
| 700 | 1 | |a Ranki, Annamari |e verfasserin |4 aut | |
| 700 | 1 | |a Krohn, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Cunningham-Rundles, Charlotte |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Naibo |e verfasserin |4 aut | |
| 700 | 1 | |a Bhagwat, Ashok S |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Kefei |e verfasserin |4 aut | |
| 700 | 1 | |a Peterson, Pärt |e verfasserin |4 aut | |
| 700 | 1 | |a Kisand, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Vuong, Bao Q |e verfasserin |4 aut | |
| 700 | 1 | |a Cerutti, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Kang |e verfasserin |4 aut | |
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