ArticleThe Journal of biological chemistry2014
Nucleotide insertions and deletions complement point mutations to massively expand the diversity created by somatic hypermutation of antibodies.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Profiling antigen-binding affinity of B cell repertoires in tumors by deep learning predicts immune-checkpoint inhibitor treatment outcomes.Nature cancer · 2025Article
- Rapid affinity optimization of an anti-TREM2 clinical lead antibody by cross-lineage immune repertoire mining.Nature communications · 2024Article
- Modular cytosine base editing promotes epigenomic and genomic modifications.Nucleic acids research · 2024Article
- DNA repair mechanisms that promote insertion-deletion events during immunoglobulin gene diversification.Science immunology · 2023Article
- Affinity maturation: highlights in the application of in vitro strategies for the directed evolution of antibodies.Emerging topics in life sciences · 2021Article
- Methods and cell-based strategies to produce antibody libraries: current state.Applied microbiology and biotechnology · 2021Review
- In vitro evolution of antibody affinity via insertional scanning mutagenesis of an entire antibody variable region.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Somatic hypermutation analysis for improved identification of B cell clonal families from next-generation sequencing data.PLoS computational biology · 2020Article
- Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens?Viruses · 2020Review
- Breaking the law: unconventional strategies for antibody diversification.Nature reviews. Immunology · 2019Review
- Cognizance of Molecular Methods for the Generation of Mutagenic Phage Display Antibody Libraries for Affinity Maturation.International journal of molecular sciences · 2019Review
- The Bayesian optimist's guide to adaptive immune receptor repertoire analysis.Immunological reviews · 2018Review
- The Use of Somatic Hypermutation for the Affinity Maturation of Therapeutic Antibodies.Methods in molecular biology (Clifton, N.J.) · 2018Article
- The Complex Interplay between DNA Injury and Repair in Enzymatically Induced Mutagenesis and DNA Damage in B Lymphocytes.International journal of molecular sciences · 2017Review
- Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates.Cell reports · 2017Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During somatic hypermutation (SHM), deamination of cytidine by activation-induced cytidine deaminase and subsequent DNA repair generates mutations within immunoglobulin V-regions. Nucleotide insertions and deletions (indels) have recently been shown to be critical for the evolution of antibody binding. Affinity maturation of 53 antibodies using in vitro SHM in a non-B cell context was compared with mutation patterns observed for SHM in vivo. The origin and frequency of indels seen during in vitro maturation were similar to that in vivo. Indels are localized to CDRs, and secondary mutations within insertions further optimize antigen binding. Structural determination of an antibody matured in vitro and comparison with human-derived antibodies containing insertions reveal conserved patterns of antibody maturation. These findings indicate that activation-induced cytidine deaminase acting on V-region sequences is sufficient to initiate authentic formation of indels in vitro and in vivo and that point mutations, indel formation, and clonal selection form a robust tripartite system for antibody evolution.
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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.