Recombinant human B cell repertoires enable screening for rare, specific, and natively paired antibodies View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-01-22

AUTHORS

Saravanan Rajan, Michael R. Kierny, Andrew Mercer, Jincheng Wu, Andrey Tovchigrechko, Herren Wu, William F. Dall′Acqua, Xiaodong Xiao, Partha S. Chowdhury

ABSTRACT

The human antibody repertoire is increasingly being recognized as a valuable source of therapeutic grade antibodies. However, methods for mining primary antibody-expressing B cells are limited in their ability to rapidly isolate rare and antigen-specific binders. Here we show the encapsulation of two million primary B cells into picoliter-sized droplets, where their cognate V genes are fused in-frame to form a library of scFv cassettes. We used this approach to construct natively paired phage-display libraries from healthy donors and drove selection towards cross-reactive antibodies targeting influenza hemagglutinin. Within 4 weeks we progressed from B cell isolation to a panel of unique monoclonal antibodies, including seven that displayed broad reactivity to different clinically relevant influenza hemagglutinin subtypes. Most isolated antibody sequences were not detected by next-generation sequencing of the paired repertoire, illustrating how this method can isolate extremely rare leads not likely found by existing technologies. More... »

PAGES

5

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s42003-017-0006-2

DOI

http://dx.doi.org/10.1038/s42003-017-0006-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100427084

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30271892


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