Frontiers in Cellular and Infection Microbiology (Mar 2023)

Efficient isolation of rare B cells using next-generation antigen barcoding

  • Jonathan Hurtado,
  • Jonathan Hurtado,
  • Jonathan Hurtado,
  • Claudia Flynn,
  • Claudia Flynn,
  • Claudia Flynn,
  • Jeong Hyun Lee,
  • Jeong Hyun Lee,
  • Jeong Hyun Lee,
  • Eugenia C. Salcedo,
  • Eugenia C. Salcedo,
  • Eugenia C. Salcedo,
  • Christopher A. Cottrell,
  • Christopher A. Cottrell,
  • Christopher A. Cottrell,
  • Christopher A. Cottrell,
  • Patrick D. Skog,
  • Dennis R. Burton,
  • Dennis R. Burton,
  • Dennis R. Burton,
  • Dennis R. Burton,
  • David Nemazee,
  • William R. Schief,
  • William R. Schief,
  • William R. Schief,
  • William R. Schief,
  • William R. Schief,
  • Elise Landais,
  • Elise Landais,
  • Elise Landais,
  • Devin Sok,
  • Devin Sok,
  • Devin Sok,
  • Bryan Briney,
  • Bryan Briney,
  • Bryan Briney,
  • Bryan Briney

DOI
https://doi.org/10.3389/fcimb.2022.962945
Journal volume & issue
Vol. 12

Abstract

Read online

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.

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