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Area of Science:

  • Immunology
  • Molecular Biology
  • Pathogen Research

Background:

  • Human memory B cells and plasma cells are crucial sources of pathogen-selected antibodies.
  • Developing methods to study the human memory antibody repertoire is vital for therapeutic antibody discovery.

Purpose of the Study:

  • To discuss a target-agnostic approach for isolating monoclonal antibodies from human B cells and plasma cells.
  • To explore how this approach advances understanding of immune responses and antibody diversification.

Main Methods:

  • High-throughput screening of antibodies from cultured B cells and plasma cells.
  • Target-agnostic interrogation of the human memory B cell repertoire.

Main Results:

  • Identification of potent and broadly neutralizing antibodies against various pathogens.
  • Advancement in understanding host-pathogen interactions and somatic mutations in antibody affinity maturation.
  • Discovery of a novel diversification mechanism involving templated non-Ig DNA insertion into antibody genes.

Conclusions:

  • The target-agnostic antibody discovery approach is effective for identifying therapeutic antibodies.
  • This method provides significant insights into the fundamental mechanisms of the human immune response.
  • A surprising new mechanism of antibody gene diversification has been uncovered, particularly in the context of malaria.