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- Title
Massively parallel single-cell B-cell receptor sequencing enables rapid discovery of diverse antigen-reactive antibodies.
- Authors
Goldstein, Leonard D.; Chen, Ying-Jiun J.; Wu, Jia; Chaudhuri, Subhra; Hsiao, Yi-Chun; Schneider, Kellen; Hoi, Kam Hon; Lin, Zhonghua; Guerrero, Steve; Jaiswal, Bijay S.; Stinson, Jeremy; Antony, Aju; Pahuja, Kanika Bajaj; Seshasayee, Dhaya; Modrusan, Zora; Hötzel, Isidro; Seshagiri, Somasekar
- Abstract
Obtaining full-length antibody heavy- and light-chain variable regions from individual B cells at scale remains a challenging problem. Here we use high-throughput single-cell B-cell receptor sequencing (scBCR-seq) to obtain accurately paired full-length variable regions in a massively parallel fashion. We sequenced more than 250,000 B cells from rat, mouse and human repertoires to characterize their lineages and expansion. In addition, we immunized rats with chicken ovalbumin and profiled antigen-reactive B cells from lymph nodes of immunized animals. The scBCR-seq data recovered 81% (n = 56/69) of B-cell lineages identified from hybridomas generated from the same set of B cells subjected to scBCR-seq. Importantly, scBCR-seq identified an additional 710 candidate lineages not recovered as hybridomas. We synthesized, expressed and tested 93 clones from the identified lineages and found that 99% (n = 92/93) of the clones were antigen-reactive. Our results establish scBCR-seq as a powerful tool for antibody discovery. Leonard Goldstein et al. use high-throughput single-cell B-cell receptor sequencing on thousands of individual B cells from rat, mouse, and human repertoires. They obtained paired full-length heavy- and light-chain variable regions, and show that this approach is a powerful tool for antibody discovery.
- Subjects
B cell receptors; IMMUNOGLOBULINS; OVALBUMINS; HYBRIDOMAS; CLONE cells
- Publication
Communications Biology, 2019, Vol 2, Issue 1, pN.PAG
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-019-0551-y