Abstract
Recently, B cells with regulatory functions suppressing T-cell immunity were identified. Inflammation in the context of sepsis is characterized by a profound immune dysfunction increasing the patient’s risk for additional infections. The impact of endotoxemia on B-cell dynamics, regulatory B cells (Breg) and its contribution to immune dysfunction is unknown. It is the aim of the present study to characterize the dynamics of the B-cell compartment and Breg in an experimental human endotoxemia model.In this randomized placebo-controlled cross-over study, 20 healthy males received an intravenous injection of endotoxin (Escherichia coli lipopolysaccharide, LPS, 0.8 ng/kg body weight) or placebo (saline 0.9%) on two otherwise identical study days. B cells were analyzed by flow cytometry at baseline and repeatedly up to 72 h after endotoxin/placebo injection.Absolute CD19+ B cells counts showed a significant decrease 3 h after endotoxin injection. Memory B cells were partially depleted from the circulation; the total number of Breg was significantly diminished 3 h after LPS challenge. Production of anti-inflammatory interleukin (IL)-10 (IL-10) by Breg was unaltered after LPS challenge. Systemic B-cell activating factor (BAFF) levels were significantly increased with a maximum after 24 h and remained increased up to 72 h post-injection.Endotoxemia causes a transient depletion of memory B cells and Breg from the circulation. However, the functional capacity of B cells to produce IL-10 is not impaired.
Highlights
Sepsis is an immune dysfunction affecting both pro- and anti-inflammatory mechanisms [1]
Under physiological circumstances, activated effector B cells may differentiate into plasma cells or memory B cells driving the humoral immune response and act as antigen-presenting cells to activate effector T cells (Teff)
Absolute CD19+ B cell (Figure 2, F = 23.79, P≤0.0001) and CD24hiCD38hi B cells with regulatory properties (Breg) counts (Figure 2, F = 16.39, P=0.0001) were significantly reduced at 3 h after LPS injection compared with the placebo injection
Summary
Sepsis is an immune dysfunction affecting both pro- and anti-inflammatory mechanisms [1]. The initial pro-inflammatory phase is characterized by an inappropriate immune response to a host pathogen followed by an anti-inflammatory phase rendering the host susceptible to secondary infections. Failure to clear and control these secondary infections is a major contributor to lethal outcome of sepsis [2]. It has been consistently shown that effector responses are severely compromised during this anti-inflammatory phase [3,4]. The impact of sepsis/systemic inflammation on B cells is not clear. An additional subset of B cells with regulatory properties (Breg) has been described with this subset being a potent inhibitor of Teff responses limiting pro-inflammatory immune responses [10,11].
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