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Full-length single-cell BCR sequencing paired with RNA sequencing reveals convergent responses to vaccination

ABSTRACT: Single-cell RNA sequencing can resolve transcriptional features from individual cells, but techniques capable of resolving the variable regions of B cell receptors (BCRs) – defining features that confer antigen specificity to B cells – 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 single-cell whole transcriptome libraries. We applied this method to produce accurate, full-length BCR sequences from cDNA of human PBMC generated following the 10x Genomics 3`GEX protocol.

ORGANISM(S): Homo sapiens

PROVIDER: GSE266697 | GEO | 2024/07/07

REPOSITORIES: GEO

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Full-length single-cell BCR sequencing paired with RNA sequencing reveals convergent responses to vaccination

Project description:Single-cell RNA sequencing can to resolve transcriptional features from large numbers of individual immune cells, but techniques capable of resolving the variable regions of B cell receptors (BCR) – defining features that confer antigen specificity to B cells – remain limited, especially from widely-used 3`-barcoded libraries. Here, we report a method that for recovering paired, full-length variable region sequences of the BCRs from 3`-barcoded single-cell whole transcriptome libraries. We first verified this method could produce accurate, full-length BCR sequences. We then applied this method to profile antigen-specific B cell responses elicited against the capsular polysaccharide of Streptococcus pneumoniae serotype 3 (ST3) by glycoconjugate vaccines in infant rhesus macaques. Using our method, we defined features of the BCR associated with specificity for the ST3 antigen and showed that these sequence characteristics 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 for profiling antigen-specific responses elicited by vaccination.

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