Single-cell analysis of B cell dysregulation in pediatric sepsis stratified by disease severity.

Sepsis is a life-threatening condition arising from a dysregulated host response to infection, characterized by a complex interplay between pro-inflammatory and anti-inflammatory immune mechanisms. B cells, that are key components of humoral immunity, are essential for antibody production, antigen presentation, and immune modulation. Sepsis is commonly associated with B cell lymphopenia, particularly in severe cases, as evidenced by a marked reduction in circulating B cells in both adult and pediatric patients. However, the mechanisms driving this depletion have not been completely understood, particularly in pediatric sepsis. In this study, we employed single-cell RNA sequencing (scRNA-seq) to profile peripheral blood leukocytes from pediatric patients with sepsis (three with mild and three with severe condition) alongside four healthy controls. Our analysis revealed a broad depletion of immune cells in sepsis, with B cells showing the most pronounced reduction and the strongest capacity to discriminate between mild and severe disease states. Subset-level analysis identified significant loss and transcriptional reprogramming of natural killer-like B cells (ΝΚΒ), MHC II