ArticleProceedings of the National Academy of Sciences of the United States of America1993
Passenger transgenes reveal intrinsic specificity of the antibody hypermutation mechanism: clustering, polarity, and specific hot spots.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 274 citations in OpenAlex.
- Continuous targeted hypermutation with a tunable mutation window.Nature communications · 2025Article
- Functions and consequences of AID/APOBEC-mediated DNA and RNA deamination.Nature reviews. Genetics · 2022Review
- Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches.Journal of visualized experiments : JoVE · 2021Article
- Position-Dependent Differential Targeting of Somatic Hypermutation.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Somatic hypermutation analysis for improved identification of B cell clonal families from next-generation sequencing data.PLoS computational biology · 2020Article
- B Cells Carrying Antigen Receptors Against Microbes as Tools for Vaccine Discovery and Design.Current topics in microbiology and immunology · 2020Review
- Targeted selection of HIV-specific antibody mutations by engineering B cell maturation.Science (New York, N.Y.) · 2019Article
- Repertoire-wide phylogenetic models of B cell molecular evolution reveal evolutionary signatures of aging and vaccination.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Mutating for Good: DNA Damage Responses During Somatic Hypermutation.Frontiers in immunology · 2019Review
- Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier.Immunity · 2018Article
- Structural Insights from HIV-Antibody Coevolution and Related Immunization Studies.AIDS research and human retroviruses · 2018Review
- Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development.Cell host & microbe · 2018Article
- HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope.Nature communications · 2018Article
- High-throughput immune repertoire analysis with IGoR.Nature communications · 2018Article
- Beyond Hot Spots: Biases in Antibody Somatic Hypermutation and Implications for Vaccine Design.Frontiers in immunology · 2018Review
- Tracing Antibody Repertoire Evolution by Systems Phylogeny.Frontiers in immunology · 2018Review
- Computational Strategies for Dissecting the High-Dimensional Complexity of Adaptive Immune Repertoires.Frontiers in immunology · 2018Review
- Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies.Science translational medicine · 2017Article
- Genetic and structural analyses of affinity maturation in the humoral response to HIV-1.Immunological reviews · 2017Review
- Gene-Specific Substitution Profiles Describe the Types and Frequencies of Amino Acid Changes during Antibody Somatic Hypermutation.Frontiers in immunology · 2017Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have analyzed somatic hypermutation in mice carrying an immunoglobulin kappa transgene in order to discriminate mutations that reflect the intrinsic specificity of the hypermutation mechanism from those highlighted by antigenic selection. We have immunized animals with three different immunogens. With one immunogen, the antigen-specific B cells express a transgenic kappa chain, which does not form part of the antibody; the transgene is a passenger free to accumulate unselected mutations. With the other two immunogens, the transgenic kappa chain constitutes the light chain of the expressed antibody. A comparison of the transgene mutations obtained under these different circumstances allows us to identify common features that we attribute to the intrinsic specificity of the hypermutation process. In particular, it yields only base substitutions and leads to hot spots occurring in individual positions (e.g., the second base of the Ser-31 codon). The mutations preferentially accumulate around the first complementarity-determining region. The process exhibits specific base substitution preferences with transitions being favored over transversions. We propose that these substitution preferences can be used to discriminate intrinsic from antigen-selected hot spots. We also note that hypermutation distinguishes between the coding and noncoding strands since pyrimidines (particularly thymidines) mutate less frequently than purines.
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Registered trials
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.