Nature Communications· 2026Q1
Continuous directed evolution using engineered human B cell lines
- 2citations
- Q1SCImago
- 2026year
Short summary
A new platform (CODE-HB) repurposes B cell somatic hypermutation (SHM) to continuously evolve cytosolic and surface-displayed proteins in human B cell lines, enabling rapid development of neutralizing antibodies against avian influenza and its escape variants.
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Key points
- Developed CODE-HB, a platform that repurposes B cell somatic hypermutation (SHM) for directed evolution.
- CODE-HB enables continuous evolution of cytosolic and surface-displayed proteins in human B cell lines.
- The platform introduces a broad mutational spectrum, including substitutions, deletions, and insertions.
- Successfully evolved neutralizing antibodies against avian influenza and its escape variants using the platform.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract The B cells of the human immune system have evolved somatic hypermutation (SHM) mechanisms that introduce mutations at the immunoglobulin genomic loci at a significantly higher frequency than the rest of the genome thereby allowing them to evolve antibody sequences without compromising fitness due to genome-wide mutations. Inspired by these observations, here we develop a continuous directed evolution platform in human B cell lines (CODE-HB) that repurposes the SHM mechanisms to a stable, non-immunoglobulin genomic locus of the human B cell lines to continuously evolve cytosolic and surface displayed proteins with a broad mutational spectrum comprising of substitutions, deletions and insertions. Using our human B cell surface display platform and CODE-HB, we evolve neutralizing antibodies targeting avian influenza and escape variants of influenza. Given the modularity and simplicity of CODE-HB, we anticipate that this platform can be used for rapidly evolving biotechnologically relevant biomolecules directly in human cells.
The authors' abstract, as published at the source. Nature Communications, 2026 · DOI ↗
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ImmunologyImmunology and Microbiology