Efficient isolation of rare B cells using next-generation antigen barcoding
Jonathan Hurtado, Claudia Flynn, Jeong Hyun Lee, Eugenia Salcedo, Christopher A. Cottrell, Patrick Skog, Dennis R. Burton, David Nemazee, William R. Schief, Elise Landais, Devin Sok, Bryan Briney
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.