ArticleProceedings of the National Academy of Sciences of the United States of America2002
Somatic hypermutation of the AID transgene in B and non-B cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 161 citations in OpenAlex.
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- Recent Advances in the Development of Monoclonal Antibodies and Next-Generation Antibodies.ImmunoHorizons · 2023Article
- Recent Progress in the Discovery and Development of Monoclonal Antibodies against Viral Infections.Biomedicines · 2022Review
- In vitro affinity maturation of broader and more-potent variants of the HIV-1-neutralizing antibody CAP256-VRC26.25.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Role of Microbial Translocation and Immune Activation in AIDS-Associated Non-Hodgkin Lymphoma Pathogenesis: What Have We Learned?Critical reviews in immunology · 2020Review
- Ex vivo evolution of human antibodies by CRISPR-X: from a naive B cell repertoire to affinity matured antibodies.BMC biotechnology · 2019Article
- Enhancers Improve the AID-Induced Hypermutation in Episomal Vector for Antibody Affinity Maturation in Mammalian Cell Display.Antibodies (Basel, Switzerland) · 2018Article
- The Common Key to Class-Switch Recombination and Somatic Hypermutation: Discovery of AID and Its Role in Antibody Gene Diversification.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Transient AID expression for in situ mutagenesis with improved cellular fitness.Scientific reports · 2018Article
- Identification of high affinity HER2 binding antibodies using CHO Fab surface display.Protein engineering, design & selection : PEDS · 2018Article
- Diversity in the Cow Ultralong CDR H3 Antibody Repertoire.Frontiers in immunology · 2018Review
- AID targeting: old mysteries and new challenges.Trends in immunology · 2015Review
- AIDing Chromatin and Transcription-Coupled Orchestration of Immunoglobulin Class-Switch Recombination.Frontiers in immunology · 2014Review
- AID and Apobec3G haphazard deamination and mutational diversity.Cellular and molecular life sciences : CMLS · 2013Review
- Simultaneous surface display and secretion of proteins from mammalian cells facilitate efficient in vitro selection and maturation of antibodies.The Journal of biological chemistry · 2013Article
- The origin of recurrent translocations in recombining lymphocytes: a balance between break frequency and nuclear proximity.Current opinion in cell biology · 2013Review
- Humanization of antibodies using heavy chain complementarity-determining region 3 grafting coupled with in vitro somatic hypermutation.The Journal of biological chemistry · 2013Article
- AID targeting is dependent on RNA polymerase II pausing.Seminars in immunology · 2012Review
- UNG shapes the specificity of AID-induced somatic hypermutation.The Journal of experimental medicine · 2012Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Somatic hypermutation (SHM) of the Ig genes is required for affinity maturation of the humoral response to foreign antigens. Activation-induced cytidine deaminase (AID), which is specifically expressed in germinal center centroblasts, is indispensable for this process. Expression of AID is sufficient to activate SHM in hybridomas, non-B cells, and Escherichia coli, suggesting that it initiates the mutational process by deaminating DNA. However, the cis-acting sequences that are responsible for targeting AID activity to the variable (V) region of Ig genes are unknown. Here we show that expression of AID in B cell lines (i.e., Burkitt's lymphoma Ramos and hybridoma P1-5) not only causes hypermutation of Ig sequences, but also of the AID transgene itself. Because it is possible that B cell-specific transacting factors bind to and recruit the "mutator" to the AID transgene, we tested whether the AID transgene can mutate in non-B cells. Indeed, we show that expression of AID in Chinese hamster ovary cells causes SHM of both the Ig and AID transgenes. These data suggest that high transcription rates alone may predispose any gene to mutation by AID but do not preclude that there are specific B cell factors that account for the extremely high rate of V mutation in vivo and its targeting to the V region.
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