A GROUNDBREAKING study has revealed how the human immune system evolves across the lifespan, uncovering age-specific changes in T and B cells and identifying a previously unrecognised “cytotoxic” B cell subset enriched in children. These findings provide critical insights into immune ageing and offer a new model to predict immune health.
The study recruited 220 healthy volunteers aged 0 to over 90 years from the Shanghai Pudong Cohort, representing 13 age groups. Researchers used single-cell RNA sequencing, single T and B cell receptor sequencing, high-throughput mass cytometry, bulk RNA sequencing, and flow cytometry to profile peripheral immune cells. Results showed that T cells were the most significantly impacted by age, with intensive rewiring of cell-cell interactions during specific life stages. For example, GNLY+CD8+ effector memory T cells exhibited the highest clonal expansion, with distinct functional signatures in children and the elderly. CD8+ MAIT cells peaked in relative abundance, clonal diversity, and antibacterial capability during adolescence before declining. Notably, a novel “cytotoxic” B cell subset, enriched in children, was identified and experimentally validated. The study also developed an immune age prediction model using lifecycle-wide single-cell data, enabling the evaluation of immune status and identification of individuals with disrupted immune function.
These findings have significant implications for clinical practice, offering a deeper understanding of immune ageing and potential biomarkers for assessing immune health. The immune age prediction model could be particularly valuable for identifying individuals at risk of immune dysfunction and guiding personalised interventions. Future research should explore how these age-related immune changes influence susceptibility to diseases and responses to treatments, paving the way for targeted therapies across the lifespan. This study not only advances our understanding of immune system evolution but also provides a valuable resource for further research into ageing and immune health.
Katheeja Imani, EMJ
Reference
Wang Y et al. Integrating single-cell RNA and T cell/B cell receptor sequencing with mass cytometry reveals dynamic trajectories of human peripheral immune cells from birth to old age. Nat Immunol. 2025;26(2):308-22.
