Evidence map›Paper›PMID 20048284›Full record

ArticleThe Journal of experimental medicine2010

Altering the spectrum of immunoglobulin V gene somatic hypermutation by modifying the active site of AID.

Meng Wang, Cristina Rada, Michael S Neuberger

Open access · greenAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 101 citations in OpenAlex.

  1. Article
  2. Article
  3. Insights on SNPs of Human Activation-Induced Cytidine Deaminase AID.International journal of molecular sciences · 2025
    Review
  4. Article
  5. Article
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  14. Article
  15. Determinants of Oligonucleotide Selectivity of APOBEC3B.Journal of chemical information and modeling · 2019
    Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review

7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Meng WangLaboratory of Molecular Biology, Medical Research Council, Cambridge CB2 0QH, England, UK.
Cristina Rada
Michael S Neuberger
Medical Research Council · GBMRC Laboratory of Molecular Biology · GB

Funding

Medical Research Council MC_U105178806
6 · The paper itself

Abstract

High-affinity antibodies are generated by somatic hypermutation with nucleotide substitutions introduced into the IgV in a semirandom fashion, but with intrinsic mutational hotspots strategically located to optimize antibody affinity maturation. The process is dependent on activation-induced deaminase (AID), an enzyme that can deaminate deoxycytidine in DNA in vitro, where its activity is sensitive to the identity of the 5'-flanking nucleotide. As a critical test of whether such DNA deamination activity underpins antibody diversification and to gain insight into the extent to which the antibody mutation spectrum is dependent on the intrinsic substrate specificity of AID, we investigated whether it is possible to change the IgV mutation spectrum by altering AID's active site such that it prefers a pyrimidine (rather than a purine) flanking the targeted deoxycytidine. Consistent with the DNA deamination mechanism, B cells expressing the modified AID proteins yield altered IgV mutation spectra (exhibiting a purine-->pyrimidine shift in flanking nucleotide preference) and altered hotspots. However, AID-catalyzed deamination of IgV targets in vitro does not yield the same degree of hotspot dominance to that observed in vivo, indicating the importance of features beyond AID's active site and DNA local sequence environment in determining in vivo hotspot dominance.

Indexed as

5' Flanking RegionAICDA (Activation-Induced Cytidine Deaminase)AnimalsAntibody AffinityCell LineCytidine DeaminaseDeaminationDNAHumansImmunoglobulin Variable RegionMiceMice, KnockoutSomatic Hypermutation, ImmunoglobulinSubstrate SpecificityAICDA (Activation-Induced Cytidine Deaminase)Cytidine DeaminaseDNAImmunoglobulin Variable Region

Identifiers

PMID20048284
PMCPMC2812546
OpenAlexW2127785417

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.