ArticleAutoimmunity2009
Lupus-prone MRL/faslpr/lpr mice display increased AID expression and extensive DNA lesions, comprising deletions and insertions, in the immunoglobulin locus: concurrent upregulation of somatic hypermutation and class switch DNA recombination.
Article in Autoimmunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Unique Features and Collateral Immune Effects of mRNA-LNP COVID-19 Vaccines: Plausible Mechanisms of Adverse Events and Complications.Pharmaceutics · 2025Review
- Preclinical models of cardiotoxicity from immune checkpoint inhibitor therapy.Basic research in cardiology · 2025Review
- The off-target effects of AID in carcinogenesis.Frontiers in immunology · 2023Review
- A Human MSH6 Germline Variant Associated With Systemic Lupus Erythematosus Induces Lupus-like Disease in Mice.ACR open rheumatology · 2022Article
- Epigenetics of the antibody and autoantibody response.Current opinion in immunology · 2020Review
- Aberrant expression of interleukin-10 and activation-induced cytidine deaminase in B cells from patients with Behçet's disease.Biomedical reports · 2017Article
- Small Molecule Inhibition of Rab7 Impairs B Cell Class Switching and Plasma Cell Survival To Dampen the Autoantibody Response in Murine Lupus.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- HSP90 inhibitors decrease AID levels and activity in mice and in human cells.European journal of immunology · 2015Article
- Epigenetics of Peripheral B-Cell Differentiation and the Antibody Response.Frontiers in immunology · 2015Review
- Genome-Wide Analysis Reveals Selective Modulation of microRNAs and mRNAs by Histone Deacetylase Inhibitor in B Cells Induced to Undergo Class-Switch DNA Recombination and Plasma Cell Differentiation.Frontiers in immunology · 2015Article
- Histone deacetylase inhibitors upregulate B cell microRNAs that silence AID and Blimp-1 expression for epigenetic modulation of antibody and autoantibody responses.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- MicroRNAs in lupus.Autoimmunity · 2014Review
- TSPAN33 is a novel marker of activated and malignant B cells.Clinical immunology (Orlando, Fla.) · 2013Article
- Epigenetics of the antibody response.Trends in immunology · 2013Review
- Regulation of Aicda expression and AID activity.Autoimmunity · 2013Review
- Potential roles of activation-induced cytidine deaminase in promotion or prevention of autoimmunity in humans.Autoimmunity · 2013Review
- Article
- Gonadal steroids and humoral immunity.Nature reviews. Endocrinology · 2013Review
- The constant region contributes to the antigenic specificity and renal pathogenicity of murine anti-DNA antibodies.Journal of autoimmunity · 2012Article
- Altered pattern of immunoglobulin hypermutation in mice deficient in Slip-GC protein.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of an array of pathogenic autoantibodies, including high-affinity anti-dsDNA IgG antibodies. These autoantibodies are mutated and class-switched, mainly to IgG, indicating that immunoglobulin (Ig) gene somatic hypermutation (SHM) and class switch DNA recombination (CSR) are important in their generation. Lupus-prone MRL/fas(lpr/lpr) mice develop a systemic autoimmune syndrome that shares many features with human SLE. We found that Ig genes were heavily mutated in MRL/fas(lpr/lpr) mice and contained long stretches of DNA deletions and insertions. The spectrum of mutations in MRL/fas(lpr/lpr) B cells was significantly altered, including increased dG/dC transitions, increased targeting of the RGYW/WRCY mutational hotspot and the WGCW AID-targeting hotspot. We also showed that MRL/fas(lpr/lpr) greatly upregulated CSR, particularly to IgG2a and IgA in B cells of the spleen, lymph nodes and Peyer's patches. In MRL/fas(lpr/lpr) mice, the significant upregulation of SHM and CSR was associated with increased expression of activation-induced cytidine deaminase (AID), which mediates DNA lesion, the first step in SHM and CSR, and translesion DNA synthesis (TLS) polymerase (pol) theta, pol eta and pol zeta, which are involved in DNA synthesis/repair process associated with SHM and, possibly, CSR. Thus, in lupus-prone MRL/fas(lpr/lpr) mice, SHM and CSR are upregulated, as a result of enhanced AID expression and, therefore, DNA lesions, and dysregulated DNA repair factors, including TLS polymerases, which are involved in the repair process of AID-mediated DNA lesions.
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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.