ArticleThe Journal of experimental medicine2000
Immunoglobulin heavy chain variable region gene replacement As a mechanism for receptor revision in rheumatoid arthritis synovial tissue B lymphocytes.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 108 citations in OpenAlex.
- Differential gene expression in dromedary camels infested with sarcoptic mange.Tropical animal health and production · 2025Article
- B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma.Nature communications · 2023Article
- Receptor editing constrains development of phosphatidyl choline-specific B cells in VCell reports · 2022Article
- VH replacement in primary immunoglobulin repertoire diversification.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
- Trials and Tribulations with VH Replacement.Frontiers in immunology · 2014Review
- Secondary mechanisms of diversification in the human antibody repertoire.Frontiers in immunology · 2013Article
- Phylogenetic conservation of the 3' cryptic recombination signal sequence (3'cRSS) in the VH genes of jawed vertebrates.Frontiers in immunology · 2012Article
- B cell receptor editing in tolerance and autoimmunity.Annals of the New York Academy of Sciences · 2011Review
- Mutation pattern of paired immunoglobulin heavy and light variable domains in chronic lymphocytic leukemia B cells.Molecular medicine (Cambridge, Mass.) · 2011Article
- Integrated mimicry of B cell antibody mutagenesis using yeast homologous recombination.Molecular biotechnology · 2011Article
- Antibodies in a heavy chain knock-in mouse exhibit characteristics of early heavy chain rearrangement.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Conserved cryptic recombination signals in Vkappa gene segments are cleaved in small pre-B cells.BMC immunology · 2009Article
- Patterns of receptor revision in the immunoglobulin heavy chains of a teleost fish.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Two distinct populations of H chain-edited B cells show differential surrogate L chain dependence.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- An activation-induced cytidine deaminase-independent mechanism of secondary VH gene rearrangement in preimmune human B cells.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease.PloS one · 2008Article
- The role of rearrangement at the second Ig heavy chain locus in maintaining B cell tolerance to DNA.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Article
- Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells.The Journal of experimental medicine · 2007Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Mature B cells can alter their antibody repertoires by several mechanisms, including immunoglobulin heavy chain variable region (V(H)) replacement. This process changes the antigen combining site by replacing a portion of the original V(H)/diversity/heavy chain joining region (V(H)DJ(H)) rearrangement with a corresponding portion of a new V(H) segment. This exchange can involve cryptic heptamer-like sequences embedded in the coding regions of V(H) genes. While studying the B lymphocytes that expand in the synovial tissues of patients with rheumatoid arthritis (RA), clones with V(H)DJ(H) variants that were apparently generated by V(H) replacement were identified with surprising frequency (approximately 8%). Examples of multiple independent V(H) replacement events occurring in distinct progeny clones were also identified. These secondary V(H) rearrangements were documented at both the cDNA and genomic DNA levels and involved several heptamer-like sequences at four distinct locations within V(H) (three sites in framework region 3 and one in complementarity determining region 2). The identification of blunt-ended double-stranded DNA breaks at the embedded heptamers and the demonstration of recombinase activating gene (RAG) expression suggested that these rearrangements could occur in the synovial tissues, presumably in pseudo-germinal centers, and that they could be mediated by RAG in a recognition signal sequence-specific manner. The presence of V(H) mutations in the clones that had undergone replacement indicated that these B cells were immunocompetent and could receive and respond to diversification signals. A relationship between these secondary V(H) gene rearrangements and the autoimmunity characteristic of RA should be considered.
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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.