ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2015
The mutation patterns in B-cell immunoglobulin receptors reflect the influence of selection acting at multiple time-scales.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 56 citations in OpenAlex.
- Machine learning in AIRR diagnostics: Advances and applications.Immunoinformatics (Amsterdam, Netherlands) · 2025Article
- A Sitewise Model of Natural Selection on Individual Antibodies via a Transformer-Encoder.Molecular biology and evolution · 2025Article
- Pediatric B cell repertoires are enriched for naive clonal phenotypes and are shaped by distinct selection dynamics.Frontiers in immunology · 2025Article
- B cell phylogenetics in the single cell era.Trends in immunology · 2024Review
- VH2+ Antigen-Experienced B Cells in the Cerebrospinal Fluid Are Expanded and Enriched in Pediatric Anti-NMDA Receptor Encephalitis.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- An anti-LpqH human monoclonal antibody from an asymptomatic individual mediates protection against Mycobacterium tuberculosis.NPJ vaccines · 2023Article
- Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity.Nature immunology · 2023Article
- Shared bias in H chain V-J pairing in naive and memory B cells.Frontiers in immunology · 2023Article
- Exploring the impact of clonal definition on B-cell diversity: implications for the analysis of immune repertoires.Frontiers in immunology · 2023Article
- Lineage Reconstruction of In Vitro Identified Antigen-Specific Autoreactive B Cells from Adaptive Immune Receptor Repertoires.International journal of molecular sciences · 2022Article
- IgTreeZ, A Toolkit for Immunoglobulin Gene Lineage Tree-Based Analysis, Reveals CDR3s Are Crucial for Selection Analysis.Frontiers in immunology · 2022Article
- Adaptive Immune Receptor Repertoire (AIRR) Community Guide to Repertoire Analysis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Translatability and transferability of in silico models: Context of use switching to predict the effects of environmental chemicals on the immune system.Computational and structural biotechnology journal · 2022Article
- A scalable model for simulating multi-round antibody evolution and benchmarking of clonal tree reconstruction methods.Frontiers in immunology · 2022Article
- Article
- Struggle within: evolution and ecology of somatic cell populations.Cellular and molecular life sciences : CMLS · 2021Review
- Distinct clonal evolution of B-cells in HIV controllers with neutralizing antibody breadth.eLife · 2021Article
- Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Using B cell receptor lineage structures to predict affinity.PLoS computational biology · 2020Article
- Repertoire-wide phylogenetic models of B cell molecular evolution reveal evolutionary signatures of aging and vaccination.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the several-week course of an immune response, B cells undergo a process of clonal expansion, somatic hypermutation of the immunoglobulin (Ig) genes and affinity-dependent selection. Over a lifetime, each B cell may participate in multiple rounds of affinity maturation as part of different immune responses. These two time-scales for selection are apparent in the structure of B-cell lineage trees, which often contain a 'trunk' consisting of mutations that are shared across all members of a clone, and several branches that form a 'canopy' consisting of mutations that are shared by a subset of clone members. The influence of affinity maturation on the B-cell population can be inferred by analysing the pattern of somatic mutations in the Ig. While global analysis of mutation patterns has shown evidence of strong selection pressures shaping the B-cell population, the effect of different time-scales of selection and diversification has not yet been studied. Analysis of B cells from blood samples of three healthy individuals identifies a range of clone sizes with lineage trees that can contain long trunks and canopies indicating the significant diversity introduced by the affinity maturation process. We here show that observed mutation patterns in the framework regions (FWRs) are determined by an almost purely purifying selection on both short and long time-scales. By contrast, complementarity determining regions (CDRs) are affected by a combination of purifying and antigen-driven positive selection on the short term, which leads to a net positive selection in the long term. In both the FWRs and CDRs, long-term selection is strongly dependent on the heavy chain variable gene family.
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