Advances in antibody discovery from human BCR repertoires.

Antibodies make up an important and growing class of compounds used for the diagnosis or treatment of disease. While traditional antibody discovery utilized immunization of animals to generate lead compounds, technological innovations have made it possible to search for antibodies targeting a given antigen within the repertoires of B cells in humans. Here we group these innovations into four broad categories: cell sorting allows the collection of cells enriched in specificity to one or more antigens; BCR sequencing can be performed on bulk mRNA, genomic DNA or on paired (heavy-light) mRNA; BCR repertoire analysis generally involves clustering BCRs into specificity groups or more in-depth modeling of antibody-antigen interactions, such as antibody-specific epitope predictions; validation of antibody-antigen interactions requires expression of antibodies, followed by antigen binding assays or epitope mapping. Together with innovations in Deep learning these technologies will contribute to the future discovery of diagnostic and therapeutic antibodies directly from humans.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Xu, Ismanto, Zhou, Saputri, Sugihara and Standley.)