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Related Experiment Video

Updated: Jul 21, 2025

Generation of Discriminative Human Monoclonal Antibodies from Rare Antigen-specific B Cells Circulating in Blood

Generation of Discriminative Human Monoclonal Antibodies from Rare Antigen-specific B Cells Circulating in Blood

Published on: February 6, 2018

Reprogramming human B cells with custom heavy chain antibodies.

Geoffrey L Rogers¹, Chun Huang¹, Atishay Mathur¹

¹Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.

Research Square

|July 28, 2023

Summary

We developed a genome editing method to engineer human B cells into antibody factories. These engineered cells can produce custom heavy chain antibodies (HCAbs) that target specific antigens for therapeutic applications.

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Last Updated: Jul 21, 2025

Generation of Discriminative Human Monoclonal Antibodies from Rare Antigen-specific B Cells Circulating in Blood

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Single-cell Screening Method for the Selection and Recovery of Antibodies with Desired Specificities from Enriched Human Memory B Cell Populations

Published on: August 22, 2019

Area of Science:

Immunology
Molecular Biology
Genetic Engineering

Background:

The immunoglobulin heavy chain (IgH) locus in B cells controls antibody production.
Reprogramming B cells offers a novel therapeutic strategy.

Approach:

Developed a genome editing platform to modify the IgH locus in human B cells.
Created custom heavy chain antibodies (HCAbs) with antigen-recognition domains linked to Fc domains.
Engineered HCAbs for differential splicing to express B cell receptor (BCR) or secreted antibody isoforms.

Key Points:

The HCAb platform is versatile, accommodating various antigen-binding domains and Fc modifications.
Edited B cells successfully expressed anti-HIV Env HCAbs, functioning as both BCRs and secreted antibodies.
Demonstrated antigen-specific B cell responses in a tonsil organoid model.

Conclusions:

Human B cells can be reprogrammed using genome editing to produce customized therapeutic molecules.
This approach enables the regulated expression of BCRs and antibodies for targeted therapies.
The strategy holds potential for *in vivo* amplification of therapeutic molecules.