Abstract
Antibodies that recognize microbial B lymphocyte superantigenic epitopes are produced constitutively with no requirement for adaptive immune maturation. We report cleavage of the Staphylococcus aureus virulence factor extracellular fibrinogen-binding protein (Efb) by catalytic antibodies produced with no exposure to the bacterium and reduction of the catalytic antibody activity following infection. IgG catalytic antibodies that specifically hydrolyzed Efb via a nucleophilic catalytic mechanism were found in the blood of healthy humans and aseptic mice free of S. aureus infection. IgG hydrolyzed peptide bonds on the C-terminal side of basic amino acids, including a bond located within the C3b-binding domain of Efb. Efb digested with the IgG lost its ability to bind C3b and inhibit complement-dependent antibody-mediated red blood cell lysis. In addition to catalysis, the IgG expressed saturable Efb binding activity. IgG from S. aureus-infected mice displayed reduced Efb cleaving activity and increased Efb binding activity compared with uninfected controls, suggesting differing effects of the infection on the antibody subsets responsible for the two activities. IgG from children hospitalized for S. aureus infection also displayed reduced Efb cleavage compared with healthy children. These data suggest a potential defense function for constitutively produced catalytic antibodies to a putative superantigenic site of Efb, but an adaptive catalytic response appears to be proscribed.
Highlights
We examined the role of catalytic antibodies in immune defense against Staphylococcus aureus
Constitutive Murine Catalytic Antibodies to extracellular fibrinogen-binding protein (Efb)—Initially, we studied whether antibodies capable of hydrolyzing Efb are produced by mice without stimulation by exogenous microbial antigens
Our studies show that specific catalytic antibodies to Efb are produced constitutively without exposure to S. aureus
Summary
We examined the role of catalytic antibodies in immune defense against Staphylococcus aureus. 9940 JOURNAL OF BIOLOGICAL CHEMISTRY reduced Efb cleavage compared with healthy children These data suggest a potential defense function for constitutively produced catalytic antibodies to a putative superantigenic site of Efb, but an adaptive catalytic response appears to be proscribed. Whether catalysis is deployed by the immune system for defense against microbes, remains a subject of debate Antibodies generally develop their noncovalent antigen binding activity over days to weeks by adaptive maturational processes driven by antigen binding to B cell receptors (BCRs) (antibodies expressed on the cell surface in association with signal transducing proteins). We report constitutively-produced antibodies that catalyze the cleavage of extracellular fibrinogen-binding protein (Efb), a secreted S. aureus virulence factor that interferes with platelet aggregation, wound healing, and complement activation (19 –22). We suggest that Efb contains a B-SAg determinant to which specific catalytic antibodies are produced as a constitutive immune function but exposure to the determinant down-regulates the B cell subset producing the catalytic antibodies
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