Pathogenesis of B-cell superantigen-induced immune complex-mediated inflammation

Infect Immun. 2006 Feb;74(2):1196-203. doi: 10.1128/IAI.74.2.1196-1203.2006.


Staphylococcal protein A (SpA) is representative of a new class of antigens, the B-cell superantigens (SAgs). These antigens bind to the Fab regions of immunoglobulin molecules outside their complementarity-determining regions. SpA, the best-studied B-cell SAg, reacts with the Fabs of most VH3+ immunoglobulins, which are expressed on 30 to 60% of human peripheral B cells. Therefore, B-cell SAgs like SpA have great potential to elicit inflammatory responses in vivo. We previously reported that the interaction of SpA with VH3+ immunoglobulin molecules leads to activation of the complement cascade and produces a histologic pattern of inflammation in the skin of a rabbit indicative of immune complex injury. To elucidate the cellular and molecular events contributing to this type of unconventional immune complex-mediated inflammation, we established a mouse peritoneal Arthus reaction model. Mice treated intravenously with human polyclonal immunoglobulin G (IgG), followed by intraperitoneal injection of SpA, showed neutrophil influx into the peritoneal cavity with peak numbers appearing at 8 h. This inflammatory reaction was dependent on the interaction of SpA with VH3+ IgG. Mast cells, FcgammaRIII, complement components, and tumor necrosis factor alpha play obligatory roles, and the reaction is associated with the local release of the CXC chemokines macrophage inflammatory protein 2 and KC. The data provide further compelling evidence for the induction of immune complex-mediated injury by a B-cell SAg and highlight important factors contributing to the pathogenesis of this novel type of inflammatory reaction.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Arthus Reaction / etiology
  • Arthus Reaction / immunology*
  • Arthus Reaction / physiopathology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Immunoglobulin Heavy Chains / administration & dosage
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin Variable Region / administration & dosage
  • Immunoglobulin Variable Region / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neutrophil Infiltration
  • Neutrophils / immunology
  • Peritoneal Cavity / physiopathology
  • Staphylococcal Protein A / administration & dosage*
  • Staphylococcal Protein A / immunology
  • Staphylococcal Protein A / metabolism
  • Superantigens / administration & dosage*
  • Superantigens / immunology
  • Superantigens / metabolism


  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Staphylococcal Protein A
  • Superantigens