Systematic analysis of B-cell repertoires

Abstract

The B-cell repertoire within an individual is a library of antibodies to all the pathogens an individual had been exposed to in the past. Many methods have been implemented to dig into this rich source of antibodies to understand the B-cell response to exposure and vaccination as well as identification of therapeutic antibodies. The advent of paired chain single-cell sequencing technology in recent years has transformed antibody discovery methods as well as repertoire characterization. With an increase in paired antibody sequence datasets, in-depth studies can be performed to understand the prevalence of public clonotypes and their implications to humoral immunity. Here, we discuss the characterization of the antibody repertoire both functionally and genetically using high throughput antibody discovery methods to characterize B-cell repertoires specific to AL amyloidosis, Influenza virus, Ebola virus, and SARS-CoV-2. A landscape of the humoral immune response against multiple pathogens was characterized. In turn, multiple antibody variable genes were identified to correspond to functional characteristics such antibody binding or neutralization to various pathogens. Recent studies have shown unrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes. Access to large datasets of paired-chain single-cell sequencing allowed for a systematic study on not only the prevalence of public clonotypes to Ebola virus and SARS-CoV-2 but the functional characteristics of public clonotypes and their implications on rational vaccine design, as well as viral escape. Altogether, this work analyzes antibody sequencing and functional characterization to understand B-cell repertoires and public clonotypes while detailing antibody evolution and sequence to function relationships.