Age-related dysregulation of B cells in acute respiratory distress syndrome

The role of B cells in distinguishing the outcomes of acute respiratory distress syndrome (ARDS) in children and adults remains unclear. We studied the transcriptomic characteristics of peripheral blood B cell alterations in children and adults with ARDS using single-cell RNA and B-cell receptor repertoire analysis. During the acute phase, adults exhibited higher neutrophil counts and lower B cell levels than children. The maturation and activation of naïve B cells were impaired in adults with ARDS by T cells and neutrophils via the MIF-CD74-PI3K-AKT pathway. Upregulated interferon-γ and interferon-α contributed to aberrant nuclear factor kappa B and Janus kinase/signal transducers and activators of transcription activation, resulting in apoptosis and pro-inflammation in plasma cells of adults and children with ARDS, respectively. Autoimmune patterns and diminished hyperexpanded clonotypes in plasma cells were similar in fatal cases of ARDS in adults and children. These findings elucidate B cell maturation, activation, and immunoglobulin patterns in ARDS, providing a foundation for prognostic assessment and B cell-targeted therapies.