AUTHOR=Hurtado Jonathan , Flynn Claudia , Lee Jeong Hyun , Salcedo Eugenia C. , Cottrell Christopher A. , Skog Patrick D. , Burton Dennis R. , Nemazee David , Schief William R. , Landais Elise , Sok Devin , Briney Bryan TITLE=Efficient isolation of rare B cells using next-generation antigen barcoding JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=12 YEAR=2023 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.962945 DOI=10.3389/fcimb.2022.962945 ISSN=2235-2988 ABSTRACT=

The ability to efficiently isolate antigen-specific B cells in high throughput will greatly accelerate the discovery of therapeutic monoclonal antibodies (mAbs) and catalyze rational vaccine development. Traditional mAb discovery is a costly and labor-intensive process, although recent advances in single-cell genomics using emulsion microfluidics allow simultaneous processing of thousands of individual cells. Here we present a streamlined method for isolation and analysis of large numbers of antigen-specific B cells, including next generation antigen barcoding and an integrated computational framework for B cell multi-omics. We demonstrate the power of this approach by recovering thousands of antigen-specific mAbs, including the efficient isolation of extremely rare precursors of VRC01-class and IOMA-class broadly neutralizing HIV mAbs.