Evidence map›Paper›PMID 37098343›Full record

ArticleCell2023

Mesoscale DNA feature in antibody-coding sequence facilitates somatic hypermutation.

Yanyan Wang, Senxin Zhang, Xinrui Yang, Joyce K Hwang, Chuanzong Zhan, Chaoyang Lian, Chong Wang, Tuantuan Gui, Binbin Wang, Xia Xie and 20 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Egyptian rousette bat humoral immunity to H9 influenza hemagglutinin.bioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 8 institutions in 3 countries.

Yanyan WangState Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Senxin ZhangDepartment of Mathematics, Shanghai Normal University, Shanghai 200234, China.
Xinrui YangKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
Joyce K HwangHoward Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Chuanzong ZhanShanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Chaoyang LianShanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Chong WangHoward Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Tuantuan GuiShanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Binbin WangShanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Xia XieState Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Pengfei DaiState Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Lu ZhangSchool of Life Sciences, Fudan University, Shanghai 200438, China.
Ying TianShanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Huizhi ZhangInstitute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Chong HanState Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Yanni CaiState Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Qian HaoShanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Xiaofei YeDepartment of Biosciences and Nutrition, Karolinska Institutet, Huddinge, 141-83 Stockholm, Sweden; Kindstar Global Precision Medicine Institute, Wuhan 430000, China.
Xiaojing LiuState Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Jiaquan LiuState Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Zhiwei CaoSchool of Life Sciences, Fudan University, Shanghai 200438, China.
Shaohui HuangInstitute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; School of Biosciences, University of Chinese Academy of Sciences, Beijing 101499, China.
Jie SongHangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
Qiang Pan-HammarströmDepartment of Biosciences and Nutrition, Karolinska Institutet, Huddinge, 141-83 Stockholm, Sweden; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Yaofeng ZhaoState Key Laboratory of Farm Animal Biotech Breeding, China Agricultural University, Beijing 100193, China.
Frederick W AltHoward Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Xiaoqi ZhengCenter for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Lin-Tai DaKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
Leng-Siew YeapShanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Center for Immune-Related Diseases at Shanghai Institute of Immunology, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: yeaplengsiew@shsmu.edu.cn.
Fei-Long MengState Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Huashen Institute of Microbes and Infections, Shanghai 200052, China. Electronic address: feilong.meng@sibcb.ac.cn.
Shanghai Jiao Tong University · CNCenter for Excellence in Molecular Cell Science · CNBoston Children's Hospital · USChinese Academy of Sciences · CNFudan University · CNKarolinska Institutet · SEChina Agricultural University · CNShanghai Normal University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Somatic hypermutation (SHM), initiated by activation-induced cytidine deaminase (AID), generates mutations in the antibody-coding sequence to allow affinity maturation. Why these mutations intrinsically focus on the three nonconsecutive complementarity-determining regions (CDRs) remains enigmatic. Here, we found that predisposition mutagenesis depends on the single-strand (ss) DNA substrate flexibility determined by the mesoscale sequence surrounding AID deaminase motifs. Mesoscale DNA sequences containing flexible pyrimidine-pyrimidine bases bind effectively to the positively charged surface patches of AID, resulting in preferential deamination activities. The CDR hypermutability is mimicable in in vitro deaminase assays and is evolutionarily conserved among species using SHM as a major diversification strategy. We demonstrated that mesoscale sequence alterations tune the in vivo mutability and promote mutations in an otherwise cold region in mice. Our results show a non-coding role of antibody-coding sequence in directing hypermutation, paving the way for the synthetic design of humanized animal models for optimal antibody discovery and explaining the AID mutagenesis pattern in lymphoma.

Indexed as

Cytidine DeaminaseSomatic Hypermutation, ImmunoglobulinAnimalsAntibodiesComplementarity Determining RegionsDNADNA, Single-StrandedEvolution, MolecularMiceMutationNucleotide MotifsAntibodiesComplementarity Determining RegionsCytidine DeaminaseDNADNA, Single-Strandedaffinity maturationAIDcomplementarity-determining regiondeaminasesomatic hypermutation

Identifiers

PMID37098343
OpenAlexW4366824424

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.