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B-cell receptors (BCRs) are membrane-bound immunoglobulins that recognize and bind foreign proteins (antigens). BCRs are formed through random somatic changes of germline DNA, creating a vast repertoire of unique sequences that enable individuals to recognize a diverse range of antigens. After encountering antigen for the first time, BCRs undergo a process of affinity maturation, whereby cycles of rapid somatic mutation and selection lead to improved antigen binding. This constitutes an accelerated evolutionary process that takes place over days or weeks. Next-generation sequencing of the gene regions that determine BCR binding has begun to reveal the diversity and dynamics of BCR repertoires in unprecedented detail. Although this new type of sequence data has the potential to revolutionize our understanding of infection dynamics, quantitative analysis is complicated by the unique biology and high diversity of BCR sequences. Models and concepts from molecular evolution and phylogenetics that have been applied successfully to rapidly evolving pathogen populations are increasingly being adopted to study BCR diversity and divergence within individuals. However, BCR dynamics may violate key assumptions of many standard evolutionary methods, as they do not descend from a single ancestor, and experience biased mutation. Here, we review the application of evolutionary models to BCR repertoires and discuss the issues we believe need be addressed for this interdisciplinary field to flourish.

Original publication

DOI

10.1093/molbev/msw015

Type

Journal article

Journal

Mol Biol Evol

Publication Date

05/2016

Volume

33

Pages

1147 - 1157

Keywords

B-cell receptor, diversity, immunoglobulin, infection., molecular evolution, Adaptive Immunity, Antibody Affinity, B-Lymphocytes, Evolution, Molecular, Genetic Variation, High-Throughput Nucleotide Sequencing, Humans, Immunoglobulins, Infection, Membrane Proteins, Mutation, Receptors, Antigen, B-Cell