B cell clonal expansion is correlated with antigen-specificity in young but not old mice

Aging of the humoral immune response has been shown to affect its critical role in defending the host from a variety of pathogens. Technical limitations have nevertheless made it challenging to investigate the relationship between genotype and phenotype of antibody repertoires in the context of aging. We therefore performed single-cell sequencing of over 95,000 B cells to simultaneously investigate B cell receptor (BCR) repertoires and gene expression profiles in the bone marrow and spleens of young and old mice following immunizations with a protein antigen. We discovered the presence of clonally expanded B cells in both young and old mice, which had distinct transcriptional phenotypes and exhibited age-associated gene signatures relating to plasma cell differentiation and protein folding and stabilization genes. Recombinant expression of 227 monoclonal antibodies revealed that clonally expanded B cells were frequently antigen-specific in young mice but not in old mice. Furthermore, we detected clonal convergence across different mice which was correlated with antigen-specificity. Although isotype- and expansion-specific transcriptional phenotypes could be detected, there was little correlation with antigen-specificity and transcriptional signatures. Together, our work provides an age-resolved single-cell repertoire resource that further relates antibody specificity, repertoire features, and whole transcriptomes.