Specific Expression of Activation-induced Cytidine Deaminase (AID), a Novel Member of the RNA-editing Deaminase Family in Germinal Center B Cells

Muramatsu, Masamichi; Sankaranand, V.S.; Anant, Shrikant; Sugai, Manabu; Kinoshita, Kazuo; Davidson, Nicholas O.; Honjo, Tasuku

doi:10.1074/jbc.274.26.18470

Cited by 1,039 publications

(870 citation statements)

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“…The discovery of activation-induced cytidine deaminase (AID) provided a clue to this problem [38][39][40] . It is now generally accepted that the deamination of cytidines into uracils by AID is the initiating event that allows the specific recruitment of factors involved in SHM, CSR or gene conversion 41 .…”

Section: Somatic Hypermutation and Dna Polymerasesmentioning

confidence: 99%

DNA polymerases in adaptive immunity

Weill

Reynaud

2008

Nat Rev Immunol

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PrefaceTo cope with an unpredictable variety of potential pathogenic insults, the immune system must generate an enormous diversity of recognition structures, and it does so by making stepwise modifications of key genetic loci in each lymphoid cell. This proceeds through the action of lymphoid-specific proteins acting together with the general DNA-repair machinery of the cell. Strikingly, these general mechanisms are usually diverted from their normal functions, being used in rather atypical ways in order to privilege diversity over accuracy. In this Review, we focus on the contribution of a set of DNA polymerases discovered in the last decade to these unique DNA transactions.

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Section: Somatic Hypermutation and Dna Polymerasesmentioning

confidence: 99%

DNA polymerases in adaptive immunity

Weill

Reynaud

2008

Nat Rev Immunol

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“…These changes in isotype can be very important, since various isotypes are distributed differently in the body, have different half-lives in the circulation and carry out distinct subsets of effector functions (Stavnezer, 2000). Both SHM and CSR require activation induced cytidine deaminase (AID), which converts deoxycytidines in the V and switch regions to uracil and initiates both processes (Muramatsu et al, 1999;Di Noia et al, 2002;Manis et al, 2002;Bransteitter et al, 2003). Patients that are genetically deficient in AID make only low affinity IgM antibodies and die of infections if they are not treated with hyperimmune immunoglobulins (Quartier et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Forced expression of AID facilitates the isolation of class switch variants from hybridoma cells

Iglesias-Ussel

Fan

et al. 2006

Journal of Immunological Methods

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Monoclonal antibodies are used in the treatment and diagnosis of diseases and to study the protective and adverse functions of antibodies in vitro and in vivo. Since the isotype determines the effector function, half-life in the serum and distribution throughout the body, it would be useful to have a battery of antibodies with the same binding site associated with different isotypes. However, since hybridomas switch isotypes at very low frequencies in tissue culture, it has been difficult and very labor intensive to isolate panels of class switch variants. We show here that stable transfection of activation-induced cytidine deaminase (AID) in hybridomas increased their frequency of switching to a level that greatly facilitated the isolation of subclones expressing monoclonal antibodies of different isotypes. Although forced expression of AID also increased the frequency of somatic hypermutation in the immunoglobulin variable regions that encode the antigen-binding site, antigen recognition was retained in the isotype switched antibodies.

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“…APOBEC4 has no ascribed function so far 6 . AID deaminates genomic ssDNA of B cells, initiating immunoglobulin somatic hypermutation and class switch processes 7– 9 . Most notably, APOBEC3 enzymes participate in innate immunity against retroviruses and endogenous retroelements 10– 12 .…”

Section: Introductionmentioning

confidence: 99%

A putative antiviral role of plant cytidine deaminases

et al. 2017

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Background: A mechanism of innate antiviral immunity operating against viruses infecting mammalian cells has been described during the last decade. Host cytidine deaminases ( e.g., APOBEC3 proteins) edit viral genomes, giving rise to hypermutated nonfunctional viruses; consequently, viral fitness is reduced through lethal mutagenesis. By contrast, sub-lethal hypermutagenesis may contribute to virus evolvability by increasing population diversity. To prevent genome editing, some viruses have evolved proteins that mediate APOBEC3 degradation. The model plant Arabidopsis thaliana genome encodes nine cytidine deaminases ( AtCDAs), raising the question of whether deamination is an antiviral mechanism in plants as well. Methods: Here we tested the effects of expression of AtCDAs on the pararetrovirus Cauliflower mosaic virus (CaMV). Two different experiments were carried out. First, we transiently overexpressed each one of the nine A. thaliana AtCDA genes in Nicotiana bigelovii plants infected with CaMV, and characterized the resulting mutational spectra, comparing them with those generated under normal conditions. Secondly, we created A. thaliana transgenic plants expressing an artificial microRNA designed to knock-out the expression of up to six AtCDA genes. This and control plants were then infected with CaMV. Virus accumulation and mutational spectra where characterized in both types of plants. Results: We have shown that the A. thaliana AtCDA1 gene product exerts a mutagenic activity, significantly increasing the number of G to A mutations in vivo, with a concomitant reduction in the amount of CaMV genomes accumulated. Furthermore, the magnitude of this mutagenic effect on CaMV accumulation is positively correlated with the level of AtCDA1 mRNA expression in the plant. Conclusions: Our results suggest that deamination of viral genomes may also work as an antiviral mechanism in plants.

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Specific Expression of Activation-induced Cytidine Deaminase (AID), a Novel Member of the RNA-editing Deaminase Family in Germinal Center B Cells

Cited by 1,039 publications

References 35 publications

DNA polymerases in adaptive immunity

DNA polymerases in adaptive immunity

Forced expression of AID facilitates the isolation of class switch variants from hybridoma cells

A putative antiviral role of plant cytidine deaminases

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