ArticleImmunology2005
Problems in using statistical analysis of replacement and silent mutations in antibody genes for determining antigen-driven affinity selection.
Article in Immunology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Constitutive production of catalytic antibodies to a Staphylococcus aureus virulence factor and effect of infection.The Journal of biological chemistry · 2012Trial
- B cell M-CLL clones retain selection against replacement mutations in their immunoglobulin gene framework regions.Frontiers in oncology · 2023Article
- IGHV mutational status of nodal marginal zone lymphoma by NGS reveals distinct pathogenic pathways with different prognostic implications.Virchows Archiv : an international journal of pathology · 2020Article
- Beyond Hot Spots: Biases in Antibody Somatic Hypermutation and Implications for Vaccine Design.Frontiers in immunology · 2018Review
- B cell repertoire expansion occurs in meningeal ectopic lymphoid tissue.JCI insight · 2016Article
- The mutation patterns in B-cell immunoglobulin receptors reflect the influence of selection acting at multiple time-scales.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2015Article
- Quantifying evolutionary constraints on B-cell affinity maturation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2015Article
- A repertoire of high-affinity monoclonal antibodies specific to S. typhi: as potential candidate for improved typhoid diagnostic.Immunologic research · 2015Article
- Integrating B cell lineage information into statistical tests for detecting selection in Ig sequences.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Models of somatic hypermutation targeting and substitution based on synonymous mutations from high-throughput immunoglobulin sequencing data.Frontiers in immunology · 2013Article
- Constant domain-regulated antibody catalysis.The Journal of biological chemistry · 2012Article
- Quantifying selection in high-throughput Immunoglobulin sequencing data sets.Nucleic acids research · 2012Article
- Article
- Detecting selection in immunoglobulin sequences.Nucleic acids research · 2011Article
- In situ B cell-mediated immune responses and tubulointerstitial inflammation in human lupus nephritis.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Toward effective HIV vaccination: induction of binary epitope reactive antibodies with broad HIV neutralizing activity.The Journal of biological chemistry · 2009Article
- Getting started in computational immunology.PLoS computational biology · 2008Review
- Correlation of molecular characteristics, isotype, and in vitro functional activity of human antipneumococcal monoclonal antibodies.Infection and immunity · 2006Article
- Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The analysis of molecular signatures of antigen-driven affinity selection of B cells is of immense use in studies on normal and abnormal B cell development. Most of the published literature compares the expected and observed frequencies of replacement (R) and silent (S) mutations in the complementarity-determining regions (CDRs) and the framework regions (FRs) of antibody genes to identify the signature of antigenic selection. The basic assumption of this statistical method is that antigenic selection creates a bias for R mutations in the CDRs and for S mutations in the FRs. However, it has been argued that the differences in intrinsic mutability among different regions of an antibody gene can generate a statistically significant bias even in the absence of any antigenic selection. We have modified the existing statistical method to include the effects of intrinsic mutability of different regions of an antibody gene. We used this method to analyse sequences of several B cell-derived monoclonals against T-dependent antigens, T-independent antigens, clones derived from lymphoma and amyloidogenic clones. Our sequence analysis indicates that even after correcting for the intrinsic mutability of antibody genes, statistical parameters fail to reflect the role of antigen-driven affinity selection in maturation of many clones. We suggest that, contrary to the basic assumption of such statistical methods, selection can act both for and against R mutations in the CDR as well as in the FR regions. In addition we have identified different methodological difficulties in the current uses of such statistical analysis of antibody genes.
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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.