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B-cell dynamics during experimental endotoxemia in humans.

Alexandra Brinkhoff1,2, Ye Zeng3, Annette Sieberichs3

  • 1Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany benjamin.wilde@uk-essen.de alexandra.brinkhoff@uk-essen.de.

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Endotoxemia temporarily reduces circulating memory B cells and regulatory B cells (Breg). However, their ability to produce anti-inflammatory IL-10 remains functional despite altered BAFF levels.

Keywords:
B-cellsBAFFEndotoxemiaLPSinflammationsepsis

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Area of Science:

  • Immunology
  • Sepsis Pathophysiology
  • B cell Biology

Background:

  • Regulatory B cells (Breg) suppress T-cell immunity.
  • Sepsis-induced inflammation causes immune dysfunction and infection risk.
  • The effect of endotoxemia on B cells and Breg is not well understood.

Purpose of the Study:

  • To investigate B cell dynamics and Breg populations during experimental human endotoxemia.
  • To assess the impact of endotoxin on B cell subsets and regulatory function.

Main Methods:

  • A randomized, placebo-controlled, cross-over study involving 20 healthy males.
  • Administration of endotoxin (lipopolysaccharide) or placebo intravenously.
  • Flow cytometry analysis of B cells and Breg at baseline and up to 72 hours post-injection.

Main Results:

  • Absolute CD19+ B cell counts decreased 3 hours post-endotoxin.
  • Memory B cells and Breg numbers were significantly reduced 3 hours after LPS challenge.
  • Interleukin-10 (IL-10) production by Breg was unaltered, while systemic BAFF levels increased.

Conclusions:

  • Endotoxemia induces a transient depletion of circulating memory B cells and Breg.
  • Despite numerical changes, the IL-10 producing capacity of Breg remains intact during endotoxemia.
  • Increased BAFF levels suggest a potential compensatory mechanism or inflammatory response.