Tracing Antibody Repertoire Evolution by Systems Phylogeny

Antibody evolution studies have been traditionally limited to either tracing a single clonal lineage (B cells derived from a single V-(D)-J recombination) over time or examining bulk functionality changes (e.g., tracing serum polyclonal antibody proteins). Studying a single B cell disregards the majority of the humoral immune response, whereas bulk functional studies lack the necessary resolution to analyze the co-existing clonal diversity. Recent advances in high-throughput sequencing (HTS) technologies and bioinformatics have made it possible to examine multiple co-evolving antibody monoclonal lineages within the context of a single repertoire. A plethora of accompanying methods and tools have been introduced in hopes of better understanding how pathogen presence dictates the global evolution of the antibody repertoire. Here, we provide a comprehensive summary of the tremendous progress of this newly emerging field of systems phylogeny of antibody responses. We present an overview encompassing the historical developments of repertoire phylogenetics, state-of-the-art tools, and an outlook on the future directions of this fast-advancing and promising field.