IL-10-producing regulatory B cells exhibit functional defects and play a protective role in severe endotoxic shock

Dysregulated host immune homeostasis in sepsis is life-threatening even after a successfully treated bacterial infection. Lipopolysaccharide (LPS) is an endotoxin that is a major contributor to the aberrant immune responses and endotoxic shock in gram-negative bacterial sepsis. However, the current knowledge of the role of B cells in endotoxic shock is limited. Here, we report that CD1d expression in B cells and the percentage of CD5⁺CD1d^hi regulatory B (Breg) cells decreased in a mouse model of endotoxic shock. Interestingly, IL-10 but not FasL expression in CD5⁺CD1d^hi Breg cells in response to endotoxin was dramatically reduced in severe septic shock mice, and the regulatory function of CD5⁺CD1d^hi Breg cells in vitro to control the Th1 response was also diminished. Adoptive transfer of CD5⁺CD1d^hi Breg cells from healthy WT mice but not IL-10 deficient mice downregulated the IFN-γ secretion in CD4⁺ T cells and conferred protection against severe endotoxic shock in vivo. Our findings demonstrate the change and notable therapeutic potential of IL-10-producing Breg cells in endotoxic shock.