Pathogenesis of B-cell superantigen-induced immune complex-mediated inflammation.
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.
Anderson
Amy L
AL
Allergy and Immunology Section, University of Pennsylvania School of Medicine, 421 Curie Boulevard, 1014 BRB II/III, Philadelphia, PA 19104, USA.
Sporici
Romeo
R
Lambris
John
J
Larosa
David
D
Levinson
Arnold I
AI
D000818:Animals; D001183:Arthus Reaction / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000008:administration & dosage / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology; D010529:Peritoneal Cavity / Q000503:physiopathology; D013205:Staphylococcal Protein A / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D018089:Superantigens / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism
D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D013205:Staphylococcal Protein A; D018089:Superantigens