The Journal of Immunology, Vol 157, Issue 3 1200-1206, Copyright © 1996 by American Association of Immunologists

ARTICLES

Complement activation by a B cell superantigen

LM Kozlowski, AM Soulika, GJ Silverman, JD Lambris and AI Levinson
Division of Allergy and Immunology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Staphylococcal protein A (SpA), acting as a B cell superantigen, binds to the Fab region of human VH3+ Igs. Using SpA abrogated of its IgG Fc binding activity (Mod SpA) as a model B cell superantigen, we determined whether such an interaction causes complement activation. Addition of Mod SpA to human serum led to complement consumption and the generation of C3a. To determine whether this complement activation 1) was due to an interaction between VH3+ Igs and the Fab binding site of SpA and 2) proceeded via the classical complement pathway, we tested a panel of monoclonal IgM proteins for the ability to hind C1q following interaction with SpA. C1q binding was restricted to SpA- reactive, VH3+ IgM proteins. To formally determine whether the binding of SpA to the reactive VH3+ IgM proteins led to complement activation, we reconstituted the serum from a hypogammaglobulinemic patient with monoclonal IgM proteins and measured complement consumption and C3a generation following the addition of Mod SpA. We observed complement consumption and C3a production only in Mod SpA-treated serum reconstituted with a VH3+, SpA-binding, IgM protein. Taken together, these results provide compelling evidence that the interaction of the Fab binding site of SpA and VH3+ Igs can lead to complement activation via the classical pathway. This novel interaction may have significant implications for the in vivo properties of a B cell superantigen.

This article has been cited by other articles:

				L.-A. Pirofski Of Mice and Men, Revisited: New Insights into an Ancient Molecule from Studies of Complement Activation by Cryptococcus neoformans. Infect. Immun., June 1, 2006; 74(6): 3079 - 3084. [Full Text] [PDF]

				A. L. Anderson, R. Sporici, J. Lambris, D. LaRosa, and A. I. Levinson Pathogenesis of B-Cell Superantigen-Induced Immune Complex-Mediated Inflammation Infect. Immun., February 1, 2006; 74(2): 1196 - 1203. [Abstract] [Full Text] [PDF]

				C. S. Goodyear and G. J. Silverman Death by a B Cell Superantigen: In Vivo VH-targeted Apoptotic Supraclonal B Cell Deletion by a Staphylococcal Toxin J. Exp. Med., May 5, 2003; 197(9): 1125 - 1139. [Abstract] [Full Text] [PDF]

				J. Hartleib, N. Kohler, R. B. Dickinson, G. S. Chhatwal, J. J. Sixma, O. M. Hartford, T. J. Foster, G. Peters, B. E. Kehrel, and M. Herrmann Protein A is the von Willebrand factor binding protein on Staphylococcus aureus Blood, September 15, 2000; 96(6): 2149 - 2156. [Abstract] [Full Text] [PDF]

				E. R. Wann, A. P. Fehringer, Y. V. Ezepchuk, P. M. Schlievert, P. Bina, R. F. Reiser, M. M. Hook, and D. Y. M. Leung Staphylococcus aureus Isolates from Patients with Kawasaki Disease Express High Levels of Protein A Infect. Immun., September 1, 1999; 67(9): 4737 - 4743. [Abstract] [Full Text] [PDF]

				M. Leonetti, J. Galon, R. Thai, C. Sautes-Fridman, G. Moine, and A. Menez Presentation of Antigen in Immune Complexes Is Boosted by Soluble Bacterial Immunoglobulin Binding Proteins J. Exp. Med., April 19, 1999; 189(8): 1217 - 1228. [Abstract] [Full Text] [PDF]

				J. O. Brubaker, Q. Li, A. O. Tzianabos, D. L. Kasper, and R. W. Finberg Mitogenic Activity of Purified Capsular Polysaccharide A from Bacteroides fragilis: Differential Stimulatory Effect on Mouse and Rat Lymphocytes In Vitro J. Immunol., February 15, 1999; 162(4): 2235 - 2242. [Abstract] [Full Text] [PDF]

				L. M. Kozlowski, W. Li, M. Goldschmidt, and A. I. Levinson In Vivo Inflammatory Response to a Prototypic B Cell Superantigen: Elicitation of an Arthus Reaction by Staphylococcal Protein A J. Immunol., June 1, 1998; 160(11): 5246 - 5252. [Abstract] [Full Text] [PDF]