B-cell dynamics during experimental endotoxemia in humans

Brinkhoff, Alexandra Inez GND; Zeng, Ye GND; Sieberichs, Annette GND; Dolff, Sebastian GND; Shilei, Xu GND; Sun, Ming GND; Engler, Harald Raimund GND; Benson, Sven GND; Korth, Johannes GND; Schedlowski, Manfred GND; Kribben, Andreas GND; Witzke, Oliver GND; Wilde, Benjamin GND

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.</br> 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.</br> 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) levelswere significantly increased with amaximum after 24 h and remained increased up to 72 h post-injection.</br> 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.

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Brinkhoff, A., Zeng, Y., Sieberichs, A., Dolff, S., Shilei, X., Sun, M., Engler, H., Benson, S., Korth, J., Schedlowski, M., Kribben, A., Witzke, O., Wilde, B., 2019. B-cell dynamics during experimental endotoxemia in humans. https://doi.org/10.1042/BSR20182347
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