An Engineered Mouse Model That Generates a Diverse Repertoire of Endogenous, High-Affinity Common Light Chain Antibodies

Yinghui Rong
23andMe, Inc.
February 8, 2024
Front Immunol
https://pubmed.ncbi.nlm.nih.gov/38390875/

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/38390875/

Research summary

This study presents the development and characterization of a common light chain mouse model, where the endogenous IGKJ cluster is replaced with a prearranged, modified murine IGKV10-96/IGKJ1 segment. The research evaluates the impact of this genetic modification on B-cell development and the generation of a diverse antibody repertoire upon immunization.

Key outcome of the study

The engineered mice exhibited normal B-cell development, and upon immunization with ovalbumin, generated an antibody repertoire with VH gene segment usage similar to wild-type mice. While light chain diversity was restricted to the prearranged IGKV10-96/IGKJ1 germline, the clonotype diversity matched that of wild-type mice. The common light chain antibodies displayed only slightly lower affinities compared to those from wild-type mice, demonstrating the model's suitability for bispecific antibody discovery.

Model

The mouse model was engineered by genOway for 23andMe. The endogenous IGKJ cluster was replaced with a prearranged IGKV10-96/IGKJ1 segment, creating a common light chain model. This genetic modification allows for the production of antibodies with a shared light chain, facilitating the discovery of bispecific antibodies.

TARGET:
Igkj cluster
Synonyms:
Immunoglobulin kappa joining region

Keywords

Antibody discovery, Bispecific antibodies, Common light chain, Genetically engineered mouse model

Technical specifications

Knockin mouse model, IGKJ cluster replacement, Prearranged IGKV10-96/IGKJ1 segment, B-cell development analysis, Immunization studies

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