Oxidation-Specific Epitopes (OSEs) Dominate the B Cell Response in Murine Polymicrobial Sepsis

Area of Science:

• Immunology
• Microbiology
• Pathophysiology

Background:

• Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
• Antibody production, including IgM and IgG, increases significantly after sepsis induction.

Purpose of the Study:

• To investigate the specificity of the antibody response during murine abdominal sepsis.
• To determine whether antibodies target bacterial or self-antigens post-sepsis.

Main Methods:

• Murine model of colon ascendens stent peritonitis (CASP) to induce sepsis.
• Analysis of serum and single B cells for antibody specificity.
• Utilized a panel of bacterial, sepsis-unrelated, and self-antigens, including oxidation-specific epitopes (OSEs).

Main Results:

• A robust increase in serum IgM and IgG antibodies was observed 14 days post-sepsis.
• Antibacterial IgM/IgG responses were rare; however, IgM antibodies were largely polyreactive.
• A significant proportion of IgM (16%) and IgG (20%) monoclonal antibodies (mAbs) targeted OSEs.

Conclusions:

• The primary B cell response in sepsis targets self-antigens, specifically OSEs.
• OSEs are key targets of both innate and adaptive immune responses during sepsis.
• This finding redefines the understanding of antibody specificities in the context of sepsis.