ArticleImmunology2009
Activation-induced deaminase heterozygous MRL/lpr mice are delayed in the production of high-affinity pathogenic antibodies and in the development of lupus nephritis.
Article in Immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Levels of base excision repair proteins in CD4Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4Journal of immunology research · 2020Article
- Aberrant expression of interleukin-10 and activation-induced cytidine deaminase in B cells from patients with Behçet's disease.Biomedical reports · 2017Article
- Functions and Malfunctions of Mammalian DNA-Cytosine Deaminases.Chemical reviews · 2016Review
- HSP90 inhibitors decrease AID levels and activity in mice and in human cells.European journal of 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
- Extension of the germinal center stage of B cell development promotes autoantibodies in BXD2 mice.Arthritis and rheumatism · 2013Article
- 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
- Critical role of activation induced cytidine deaminase in experimental autoimmune encephalomyelitis.Autoimmunity · 2013Article
- 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
- Activation-induced deaminase contributes to the antibody-independent role of B cells in the development of autoimmunity.Autoimmunity · 2012Article
- Altered Ig hypermutation pattern and frequency in complementary mouse models of DNA polymerase ζ activity.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Article
- Inhibition of the catalytic function of activation-induced cytidine deaminase promotes apoptosis of germinal center B cells in BXD2 mice.Arthritis and rheumatism · 2011Article
- Activation-induced deaminase-deficient MRL/lpr mice secrete high levels of protective antibodies against lupus nephritis.Arthritis and rheumatism · 2011Article
- Activation-induced cytidine deaminase and aberrant germinal center selection in the development of humoral autoimmunities.The American journal of pathology · 2011Review
- Speckled-like pattern in the germinal center (SLIP-GC), a nuclear GTPase expressed in activation-induced deaminase-expressing lymphomas and germinal center B cells.The Journal of biological chemistry · 2009Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We previously reported that activation-induced deaminase (AID) heterozygous MRL/lpr mice have substantially lower levels of serum anti-dsDNA autoantibodies than AID wild-type littermates. Given the known functions of AID, here we examined whether this decrease in pathogenic autoantibodies in the heterozygotes was the result of a defect in class switch recombination, somatic hypermutation, or both. We report significant impairment of switch recombination to most isotypes except immunoglobulin G3 (IgG3) in vitro. However, serum levels of IgG were similar to AID wild-type levels even in very young mice. Mutation accumulation in the B cells from Peyer's patches also revealed reduced somatic hypermutation in the heterozygotes. Unlike the switch defect, the hypermutation defect probably resulted in an in vivo effect because the serum IgG antibodies from the heterozygotes were of strikingly lower affinity to dsDNA than serum IgG antibodies from wild-type littermates. This suggests that the somatic hypermutation defect resulted in impaired affinity maturation of autoantibodies in these mice and explains the low levels of specific anti-dsDNA antibodies in the heterozygotes. This correlated with a delay in the development of kidney damage. These results imply that AID levels impact the class switch recombination and somatic hypermutation mechanisms and directly implicate affinity maturation of autoantibodies in autoimmunity.
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