ArticleGenome research2020
V(DD)J recombination is an important and evolutionarily conserved mechanism for generating antibodies with unusually long CDR3s.
Article in Genome research, 2020. 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, 22 citations in OpenAlex.
- Comprehensive characterization of V(D)J recombination from long-read transcriptomic data with VDJcraft.bioRxiv : the preprint server for biology · 2026Article
- Explore antibody repertoire in the era of AI.Acta biochimica et biophysica Sinica · 2025Article
- ALIGaToR: A tool for the automated annotation of immunoglobulin and T cell receptor genomic loci.bioRxiv : the preprint server for biology · 2025Article
- GenomeDecoder: inferring segmental duplications in highly repetitive genomic regions.Bioinformatics (Oxford, England) · 2025Article
- Unveiling inverted D genes and D-D fusions in human antibody repertoires unlocks novel antibody diversity.Communications biology · 2025Article
- ALIGaToR: a tool for the automated annotation of immunoglobulin and T cell receptor genomic loci.Oxford open immunology · 2025Article
- UniAligner: a parameter-free framework for fast sequence alignment.Nature methods · 2023Article
- Novel bimodal TRBD1-TRBD2 rearrangements with dual or absent D-region contribute to TRB V-(D)-J combinatorial diversity.Frontiers in immunology · 2023Article
- Insights into IGH clonal evolution in BCP-ALL: frequency, mechanisms, associations, and diagnostic implications.Frontiers in immunology · 2023Article
- Functional antibodies exhibit light chain coherence.Nature · 2022Article
- Inference of B cell clonal families using heavy/light chain pairing information.PLoS computational biology · 2022Article
- Gene prediction in the immunoglobulin loci.Genome research · 2022Article
- Organization and Complexity of the Yak (Bos Grunniens) Immunoglobulin Loci.Frontiers in immunology · 2022Article
- Individualized VDJ recombination predisposes the available Ig sequence space.Genome research · 2021Article
- Immunoglobulin germline gene variation and its impact on human disease.Genes and immunity · 2021Review
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
The V(DD)J recombination is currently viewed as an aberrant and inconsequential variant of the canonical V(D)J recombination. Moreover, since the classical 12/23 rule for the V(D)J recombination fails to explain the V(DD)J recombination, the molecular mechanism of tandem D-D fusions has remained unknown since they were discovered three decades ago. Revealing this mechanism is a biomedically important goal since tandem fusions contribute to broadly neutralizing antibodies with ultralong CDR3s. We reveal previously overlooked cryptic nonamers in the recombination signal sequences of human IGHD genes and demonstrate that these nonamers explain the vast majority of tandem fusions in human repertoires. We further reveal large clonal lineages formed by tandem fusions in antigen-stimulated immunosequencing data sets, suggesting that such data sets contain many more tandem fusions than previously thought and that about a quarter of large clonal lineages with unusually long CDR3s are generated through tandem fusions. Finally, we developed the SEARCH-D algorithm for identifying D genes in mammalian genomes and applied it to the recently completed Vertebrate Genomes Project assemblies, nearly doubling the number of mammalian species with known D genes. Our analysis revealed cryptic nonamers in RSSs of many mammalian genomes, thus demonstrating that the V(DD)J recombination is not a "bug" but an important feature preserved throughout mammalian evolution.
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