Impaired B-Cell Maturation Contributes to Reduced B Cell Numbers and Poor Prognosis in Sepsis

BACKGROUND: Reduced B cell numbers plays a critical role in sepsis immunosuppression. The role of B-cell maturation regulated by T follicular helper (Tfh) cells in reduced B cell numbers during sepsis remains unclear. We tested the hypothesis that impaired B-cell maturation contributes to reduced B cell numbers. DESIGN: Retrospective study and observational prospective cohort study. SETTINGS: Critical care units. METHODS: To identify the exact lymphocyte counts that affect the prognosis of sepsis, we firstly conducted a retrospective study. Then in the prospective cohort study, differences in B-cell maturation, B cell death and numbers of circulating Tfh (cTfh) cell were compared between 28-day survivors and 28-day non-survivors, mainly by flow cytometry and enzyme-linked immunosorbent assay. MAIN RESULTS: In retrospective study (n = 123), we found patients with lymphocyte counts less than 0.4 × 10 cells/L had higher mortality than patients with lymphocyte counts above 0.4 × 10 cells/L. In observational prospective cohort study (n = 40), compared to survivors, non-survivors had fewer numbers of mature B cell and circulating Tfh (cTfh) cell (sepsis onset: memory B cells: 3.44% vs. 4.48%, antibody-secreting cells: 4.53% vs. 6.30%, cTfh cells: 3.57% vs. 4.49%; 24 h after sepsis onset: memory B cells: 4.05% vs. 7.20%, antibody-secreting cells: 5.25% vs. 8.78%, cTfh cells: 3.98% vs. 6.15%), while there were no differences in cell death of mature B cells between them. We further noticed the numbers of cTfh cell positively correlated with the numbers of mature B cell and immunoglobulin concentrations. CONCLUSIONS: Impaired B-cell maturation contributes to reduced B cell numbers, while the numbers of cTfh cell, acting as a warning indicator for sepsis prognosis, may be a new therapeutic target for treating sepsis.