ArticleProceedings of the National Academy of Sciences of the United States of America2001
Expression of error-prone polymerases in BL2 cells activated for Ig somatic hypermutation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 68 citations in OpenAlex.
- Quantitative modeling of signaling in aggressive B cell lymphoma unveils conserved core network.PLoS computational biology · 2024Article
- For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases.International journal of molecular sciences · 2023Review
- Article
- Expression of Constitutive Fusion of Ubiquitin to PCNA Restores the Level of Immunoglobulin A/T Mutations During Somatic Hypermutation in the Ramos Cell Line.Frontiers in immunology · 2022Article
- Trans-Lesion DNA Polymerases May Be Involved in Yeast Meiosis.G3 (Bethesda, Md.) · 2013Article
- Negligible impact of pol iota expression on the alkylation sensitivity of pol beta-deficient mouse fibroblast cells.DNA repair · 2008Article
- Known components of the immunoglobulin A:T mutational machinery are intact in Burkitt lymphoma cell lines with G:C bias.Molecular immunology · 2007Article
- Down-regulation of DNA polymerase beta accompanies somatic hypermutation in human BL2 cell lines.DNA repair · 2007Article
- Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- DNA replication to aid somatic hypermutation.Advances in experimental medicine and biology · 2007Review
- Antibody diversification: mutational mechanisms and oncogenesis.Immunologic research · 2006Review
- DNA polymerases and somatic hypermutation of immunoglobulin genes.EMBO reports · 2005Review
- Hepatitis C virus E2-CD81 interaction induces hypermutation of the immunoglobulin gene in B cells.Journal of virology · 2005Article
- Expression of human AID in yeast induces mutations in context similar to the context of somatic hypermutation at G-C pairs in immunoglobulin genes.BMC immunology · 2005Article
- Lineage specificity of gene expression patterns.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- Germinal center-associated nuclear protein contributes to affinity maturation of B cell antigen receptor in T cell-dependent responses.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- Msh2 ATPase activity is essential for somatic hypermutation at a-T basepairs and for efficient class switch recombination.The Journal of experimental medicine · 2003Article
- 129-derived strains of mice are deficient in DNA polymerase iota and have normal immunoglobulin hypermutation.The Journal of experimental medicine · 2003Article
- Somatic hypermutation of the B cell receptor genes B29 (Igbeta, CD79b) and mb1 (Igalpha, CD79a).Proceedings of the National Academy of Sciences of the United States of America · 2003Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
High affinity antibodies are generated in mice and humans by means of somatic hypermutation (SHM) of variable (V) regions of Ig genes. Mutations with rates of 10(-5)--10(-3) per base pair per generation, about 10(6)-fold above normal, are targeted primarily at V-region hot spots by unknown mechanisms. We have measured mRNA expression of DNA polymerases iota, eta, and zeta by using cultured Burkitt's lymphoma (BL)2 cells. These cells exhibit 5-10-fold increases in heavy-chain V-region mutations targeted only predominantly to RGYW (R = A or G, Y = C or T, W = T or A) hot spots if costimulated with T cells and IgM crosslinking, the presumed in vivo requirements for SHM. An approximately 4-fold increase pol iota mRNA occurs within 12 h when cocultured with T cells and surface IgM crosslinking. Induction of pols eta and zeta occur with T cells, IgM crosslinking, or both stimuli. The fidelity of pol iota was measured at RGYW hot- and non-hot-spot sequences situated at nicks, gaps, and double-strand breaks. Pol iota formed T x G mispairs at a frequency of 10(-2), consistent with SHM-generated C to T transitions, with a 3-fold increased error rate in hot- vs. non-hot-spot sequences for the single-nucleotide overhang. The T cell and IgM crosslinking-dependent induction of pol iota at 12 h may indicate an SHM "triggering" event has occurred. However, pols iota, eta, and zeta are present under all conditions, suggesting that their presence is not sufficient to generate mutations because both T cell and IgM stimuli are required for SHM induction.
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