Full-length single-cell BCR sequencing paired with RNA sequencing reveals convergent responses to pneumococcal vaccination
Single-cell RNA sequencing (scRNA-seq) can resolve transcriptional features from individual cells, but scRNA-seq techniques capable of resolving the variable regions of B cell receptors (BCRs) remain limited, especially from widely-used 3'-barcoded libraries. Here, we report a method that can recover paired, full-length variable region sequences of BCRs from 3'-barcoded scRNA-seq libraries. We first verify this method (B3E-seq) can produce accurate, full-length BCR sequences. We then apply this method to profile B cell responses elicited against the capsular polysaccharide of Streptococcus pneumoniae serotype 3 (ST3) by glycoconjugate vaccines in five infant rhesus macaques. We identify BCR features associated with specificity for the ST3 antigen which are present in multiple vaccinated monkeys, indicating a convergent response to vaccination. These results demonstrate the utility of our method to resolve key features of the B cell repertoire and profile antigen-specific responses elicited by vaccination.
Authors
- J. Christopher Love (ORCID: https://orcid.org/0000-0003-0921-3144)
- Jin Hwan Kim (ORCID: https://orcid.org/0000-0002-1632-2421)
- Ognjen Sekulović (ORCID: https://orcid.org/0000-0003-1006-0595)
- Jakob Loschko
- Naveen Surendran (ORCID: https://orcid.org/0000-0003-3811-7282)
- Isis Kanevsky (ORCID: https://orcid.org/0000-0001-9173-9377)
- Duncan M. Morgan (ORCID: https://orcid.org/0000-0002-3253-1362)
- Laurent Chorro
- Yiming J. Zhang (ORCID: https://orcid.org/0000-0002-8102-3815)
- Darrell J. Irvine (ORCID: https://orcid.org/0000-0002-8637-1405)
- Ellie Feng (ORCID: https://orcid.org/0009-0002-4900-4814)
- Shuting Shi (ORCID: https://orcid.org/0000-0001-8377-1625)
- Sarita U. Patil
- MaryAnn Murillo
- Suddham Singh
Institutions
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Pfizer (United States) (US)
- Regeneron (United States) (US)
- Massachusetts General Hospital (US)
- Deerfield (United States) (US)
- IIT@MIT (US)
- Allen Institute (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-09-28
- DOI
- https://doi.org/10.1038/s42003-024-06823-0
- Citations
- 6
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 1.44
Funders
- Charles H. Hood Foundation
- Pfizer
- Dana-Farber/Harvard Cancer Center
- National Cancer Center
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- National Institutes of Health
- National Cancer Institute