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Gene Conversion-Like Events in the Diversification of Human Rearranged IGHV3-23*01 Gene Sequences

Overview of attention for article published in Frontiers in immunology, January 2012
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Title
Gene Conversion-Like Events in the Diversification of Human Rearranged IGHV3-23*01 Gene Sequences
Published in
Frontiers in immunology, January 2012
DOI 10.3389/fimmu.2012.00158
Pubmed ID
Authors

Bhargavi Duvvuri, Gillian E. Wu

Abstract

Gene conversion (GCV), a mechanism mediated by activation-induced cytidine deaminase (AID) is well established as a mechanism of immunoglobulin diversification in a few species. However, definitive evidence of GCV-like events in human immunoglobulin genes is scarce. The lack of evidence of GCV in human rearranged immunoglobulin gene sequences is puzzling given the presence of highly similar germline donors and the presence of all the enzymatic machinery required for GCV. In this study, we undertook a computational analysis of rearranged IGHV3-23(*)01 gene sequences from common variable immunodeficiency (CVID) patients, AID-deficient patients, and healthy individuals to survey "GCV-like" activities. We analyzed rearranged IGHV3-23(*)01 gene sequences obtained from total PBMC RNA and single-cell polymerase chain reaction of individual B cell lysates. Our search identified strong evidence of GCV-like activity. We observed that GCV-like tracts are flanked by AID hotspot motifs. Structural modeling of IGHV3-23(*)01 gene sequence revealed that hypermutable bases flanking GCV-like tracts are in the single stranded DNA (ssDNA) of stable stem-loop structures (SLSs). ssDNA is inherently fragile and also an optimal target for AID. We speculate that GCV could have been initiated by the targeting of hypermutable bases in ssDNA state in stable SLSs, plausibly by AID. We have observed that the frequency of GCV-like events is significantly higher in rearranged IGHV3-23-(*)01 sequences from healthy individuals compared to that of CVID patients. We did not observe GCV-like events in rearranged IGHV3-23-(*)01 sequences from AID-deficient patients. GCV, unlike somatic hypermutation (SHM), can result in multiple base substitutions that can alter many amino acids. The extensive changes in antibody affinity by GCV-like events would be instrumental in protecting humans against pathogens that diversify their genome by antigenic shift.

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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 30 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 11 37%
Student > Ph. D. Student 5 17%
Other 2 7%
Student > Doctoral Student 2 7%
Professor > Associate Professor 2 7%
Other 4 13%
Unknown 4 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 9 30%
Biochemistry, Genetics and Molecular Biology 7 23%
Immunology and Microbiology 4 13%
Nursing and Health Professions 1 3%
Arts and Humanities 1 3%
Other 2 7%
Unknown 6 20%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 July 2014.
All research outputs
#16,046,765
of 25,373,627 outputs
Outputs from Frontiers in immunology
#16,699
of 31,513 outputs
Outputs of similar age
#163,292
of 250,087 outputs
Outputs of similar age from Frontiers in immunology
#107
of 275 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 31,513 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one is in the 42nd percentile – i.e., 42% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 250,087 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 275 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.