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

Front Immunol. 2020 Jul 31:11:1570. doi: 10.3389/fimmu.2020.01570. eCollection 2020.

Abstract

In murine abdominal sepsis by colon ascendens stent peritonitis (CASP), a strong increase in serum IgM and IgG antibodies was observed, which reached maximum values 14 days following sepsis induction. The specificity of this antibody response was studied in serum and at the single cell level using a broad panel of bacterial, sepsis-unrelated as well as self-antigens. Whereas an antibacterial IgM/IgG response was rarely observed, studies at the single-cell level revealed that IgM antibodies, in particular, were largely polyreactive. Interestingly, at least 16% of the IgM mAbs and 20% of the IgG mAbs derived from post-septic mice showed specificity for oxidation-specific epitopes (OSEs), which are known targets of the innate/adaptive immune response. This identifies those self-antigens as the main target of B cell responses in sepsis.

Keywords: B cell response; CASP; oxidation-specific epitopes; polymicrobial sepsis; polyreactive antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • Autoimmunity
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Biomarkers
  • Disease Models, Animal
  • Epitopes, B-Lymphocyte / genetics
  • Epitopes, B-Lymphocyte / immunology*
  • Female
  • Immunodominant Epitopes / genetics
  • Immunodominant Epitopes / immunology*
  • Immunoglobulin G / blood
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • Immunoglobulin M / blood
  • Immunoglobulin M / genetics
  • Immunoglobulin M / immunology
  • Immunohistochemistry
  • Mice
  • Mutation
  • Oxidation-Reduction*
  • Sepsis / etiology*
  • Sepsis / metabolism*
  • V(D)J Recombination

Substances

  • Autoantibodies
  • Autoantigens
  • Biomarkers
  • Epitopes, B-Lymphocyte
  • Immunodominant Epitopes
  • Immunoglobulin G
  • Immunoglobulin M