ArticleProceedings of the National Academy of Sciences of the United States of America1998
Somatic hypermutation of the new antigen receptor gene (NAR) in the nurse shark does not generate the repertoire: possible role in antigen-driven reactions in the absence of germinal centers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Evolutionary Comparative Analyses of DNA-Editing Enzymes of the Immune System: From 5-Dimensional Description of Protein Structures to Immunological Insights and Applications to Protein Engineering.Frontiers in immunology · 2021Pooled it
- The Janus (dual) model of immunoglobulin isotype evolution: Conservation and plasticity are the defining paradigms.Immunological reviews · 2024Review
- Cold-blooded vertebrates evolved organized germinal center-like structures.Science immunology · 2023Article
- Construction of Semisynthetic Shark vNAR Yeast Surface Display Antibody Libraries.Methods in molecular biology (Clifton, N.J.) · 2023Article
- 450 million years in the making: mapping the evolutionary foundations of germinal centers.Frontiers in immunology · 2023Review
- Heavy chain-only antibody genes in fish evolved to generate unique CDR3 repertoire.European journal of immunology · 2022Article
- The immunoglobulins of cartilaginous fishes.Developmental and comparative immunology · 2021Review
- Lost structural and functional inter-relationships between Ig and TCR loci in mammals revealed in sharks.Immunogenetics · 2021Review
- Nurse shark T-cell receptors employ somatic hypermutation preferentially to alter alpha/delta variable segments associated with alpha constant region.European journal of immunology · 2020Article
- Diagnostic and therapeutic potential of shark variable new antigen receptor (VNAR) single domain antibody.International journal of biological macromolecules · 2020Review
- Ancient Use of Ig Variable Domains Contributes Significantly to the TCRδ Repertoire.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Diversity of Immunoglobulin (Ig) Isotypes and the Role of Activation-Induced Cytidine Deaminase (AID) in Fish.Molecular biotechnology · 2018Review
- Single Domain Antibodies as New Biomarker Detectors.Diagnostics (Basel, Switzerland) · 2017Review
- Biochemical Regulatory Features of Activation-Induced Cytidine Deaminase Remain Conserved from Lampreys to Humans.Molecular and cellular biology · 2017Article
- Fish Immunoglobulins.Biology · 2016Review
- Review
- Article
- The immunoglobulins of cold-blooded vertebrates.Biomolecules · 2014Review
- Construction of an artificially randomized IgNAR phage display library: screening of variable regions that bind to hen egg white lysozyme.Marine biotechnology (New York, N.Y.) · 2013Article
- The multiple shark Ig H chain genes rearrange and hypermutate autonomously.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The new antigen receptor (NAR) gene in the nurse shark diversifies extensively by somatic hypermutation. It is not known, however, whether NAR somatic hypermutation generates the primary repertoire (like in the sheep) or rather is used in antigen-driven immune responses. To address this issue, the sequences of NAR transmembrane (Tm) and secretory (Sec) forms, presumed to represent the primary and secondary repertoires, respectively, were examined from the peripheral blood lymphocytes of three adult nurse sharks. More than 40% of the Sec clones but fewer than 11% of Tm clones contained five mutations or more. Furthermore, more than 75% of the Tm clones had few or no mutations. Mutations in the Sec clones occurred mostly in the complementarity-determining regions (CDR) with a significant bias toward replacement substitutions in CDR1; in Tm clones there was no significant bias toward replacements and only a low level of targeting to the CDRs. Unlike the Tm clones where the replacement mutational pattern was similar to that seen for synonymous changes, Sec replacements displayed a distinct pattern of mutations. The types of mutations in NAR were similar to those found in mouse Ig genes rather than to the unusual pattern reported for shark and Xenopus Ig. Finally, an oligoclonal family of Sec clones revealed a striking trend toward acquisition of glutamic/aspartic acid, suggesting some degree of selection. These data strongly suggest that hypermutation of NAR does not generate the repertoire, but instead is involved in antigen-driven immune responses.
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