Senescent B cells drive COPD lung damage via altered signaling

Researchers identified B-cell senescence as a key driver of chronic obstructive pulmonary disease (COPD) by analyzing 121,885 lung cells, finding significant enrichment of senescence gene signatures in B cells from COPD patients. The senescent B cells showed impaired differentiation, increased inflammatory signaling, and lipid metabolism dysregulation, validated by spatial transcriptomics and proteomics. Distinct senescent niches with persistent inflammation and altered cell-cell communication were found in COPD lungs. Notably, enhanced ADGRE5-CD55 signaling between B cells and alveolar type II cells was observed, offering new mechanistic insights and potential therapeutic targets for this debilitating smoking-related lung disease.