This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Anderson, A. L. Articles by Levinson, A. I. Search for Related Content PubMed PubMed Citation Articles by Anderson, A. L. Articles by Levinson, A. I.

 Previous Article  |  Next Article 

Infection and Immunity, February 2006, p. 1196-1203, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1196-1203.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Pathogenesis of B-Cell Superantigen-Induced Immune Complex-Mediated Inflammation

Amy L. Anderson,¹ Romeo Sporici,^1, John Lambris,² David LaRosa,³ and Arnold I. Levinson^1,3*

Allergy and Immunology Section, Philadelphia Veterans' Administration Medical Center,¹ Department of Laboratory Medicine and Pathology,² Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104³

Received 22 September 2005/ Returned for modification 26 October 2005/ Accepted 30 November 2005

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 V_H3⁺ 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 V_H3⁺ 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 V_H3⁺ IgG. Mast cells, FcRIII, 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.

---

* Corresponding author. Mailing address: Allergy and Immunology Section, University of Pennsylvania School of Medicine, 421 Curie Boulevard, 1014 BRB II/III, Philadelphia, PA 19104. Phone: (215) 898-4592. Fax: (215) 898-0193. E-mail: frog{at}mail.med.upenn.edu.

Editor: F. C. Fang

Present address: Department of Physiology, University of Kentucky, Lexington, KY 40536.

---

Infection and Immunity, February 2006, p. 1196-1203, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1196-1203.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Montes, C. L., Acosta-Rodriguez, E. V., Merino, M. C., Bermejo, D. A., Gruppi, A. (2007). Polyclonal B cell activation in infections: infectious agents' devilry or defense mechanism of the host?. J. Leukoc. Biol. 82: 1027-1032 [Abstract] [Full Text]