Evidence map›Paper›PMID 31375545›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2019

Clustered Mutations at the Murine and Human IgH Locus Exhibit Significant Linkage Consistent with Templated Mutagenesis.

Gordon A Dale, Daniel J Wilkins, Caitlin D Bohannon, Dario Dilernia, Eric Hunter, Trevor Bedford, Rustom Antia, Ignacio Sanz, Joshy Jacob

Abstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

9 authors.

Gordon A DaleEmory Vaccine Center, Yerkes National Primate Center, Emory University, Atlanta, GA 30329.ORCID 0000-0002-4995-6017
Daniel J WilkinsEmory Vaccine Center, Yerkes National Primate Center, Emory University, Atlanta, GA 30329.ORCID 0000-0003-0398-8715
Caitlin D BohannonEmory Vaccine Center, Yerkes National Primate Center, Emory University, Atlanta, GA 30329.
Dario DilerniaEmory Vaccine Center, Yerkes National Primate Center, Emory University, Atlanta, GA 30329.
Eric HunterEmory Vaccine Center, Yerkes National Primate Center, Emory University, Atlanta, GA 30329.ORCID 0000-0002-4273-8631
Trevor BedfordDepartment of Epidemiology, School of Public Health, University of Washington, Seattle, WA 98195.
Rustom AntiaDepartment of Biology, Emory University, Atlanta, GA 30322; and.ORCID 0000-0001-7991-614X
Ignacio SanzLowance Center for Human Immunology, Department of Medicine, Emory University, Atlanta, GA 30322.
Joshy JacobEmory Vaccine Center, Yerkes National Primate Center, Emory University, Atlanta, GA 30329; jjacob3@emory.edu.ORCID 0000-0003-0247-7016

Funding

Systems Biological Analysis of Innate and Adaptive Responses to VaccinationU19AI090023 · NIAID · EMORY UNIVERSITY · PI AHMED, RAFI, LI, SHUZHAO · 2010 to 2021
$45.0M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008169 · NIGMS · EMORY UNIVERSITY · PI GROSS, ROBERT E · 1987 to 2021
$20.3M
Modeling the dynamics and evolution of immune responses to influenza virusesU19AI117891 · NIAID · EMORY UNIVERSITY · PI AHMED, RAFI, ANTIA, RUSTOM NOSHIR · 2015 to 2019
$8.4M
Relevance of Tracts of Framework Mutations in IgM Plasma CellsF30AI124568 · NIAID · EMORY UNIVERSITY · PI DALE, GORDON ALEXANDER · 2016 to 2018
$147k
NIAID NIH HHS F30 AI124568NIAID NIH HHS U19 AI090023NIAID NIH HHS U19 AI117891NIGMS NIH HHS T32 GM008169
6 · The paper itself

Abstract

Somatic hypermutation generates a myriad of Ab mutants in Ag-specific B cells, from which high-affinity mutants are selected. Chickens, sheep, and rabbits use nontemplated point mutations and templated mutations via gene conversion to diversify their expressed Ig loci, whereas mice and humans rely solely on untemplated somatic point mutations. In this study, we demonstrate that, in addition to untemplated point mutations, templated mutagenesis readily occurs at the murine and human Ig loci. We provide two distinct lines of evidence that are not explained by the Neuberger model of somatic hypermutation: 1) across multiple data sets there is significant linkage disequilibrium between individual mutations, especially among close mutations, and 2) among those mutations, those <8 bp apart are significantly more likely to match microhomologous regions in the IgHV repertoire than predicted by the mutation profiles of somatic hypermutation. Together, this supports the role of templated mutagenesis during somatic diversification of Ag-activated B cells.

Indexed as

Genetic LinkageGenetic LociMutagenesisSomatic Hypermutation, ImmunoglobulinAnimalsDNA-Binding ProteinsDNA HelicasesGerminal CenterHumansImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionMiceMice, Inbred BALB CMice, Inbred C57BLMutationPlasma CellsDNA-Binding ProteinsDNA HelicasesImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionRAD54L protein, human

Identifiers

PMID31375545
PMCPMC6702052

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Registered trials

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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.