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In Vivo Inflammatory Response to a Prototypic B Cell Superantigen: Elicitation of an Arthus Reaction by Staphylococcal Protein A¹

Lisa M. Kozlowski^2,*, Weiping Li^*, Michael Goldschmidt and Arnold I. Levinson^3,*

^* Division of Allergy and Immunology, University of Pennsylvania School of Medicine and Laboratory of Pathology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104

Staphylococcal protein A (SpA) is representative of a new class of Ags, the B cell superantigens (SAgs). These SAgs, unlike conventional Ags, bind to the Fab regions of Ig molecules outside their complementarity-determining regions. In addition, B cell SAgs can react with a substantial amount of a host’s serum Igs by virtue of their ability to interact with many members of an entire variable heavy chain (V_H) or variable light chain gene family. For example, SpA reacts with the Fabs of most human Igs using heavy chains from the V_H3 gene family (V_H3⁺). Members of this gene family are expressed on 30 to 60% of human peripheral B cells. We sought to determine whether the interaction of a B cell SAg with its reactive Igs can elicit immune complex-mediated tissue injury. Using the Arthus reaction in rabbits as an in vivo model of immune complex-mediated tissue inflammation, we demonstrated that untreated rabbits, which were administered SpA intradermally (i.d.), do not develop a cutaneous inflammatory response. However, when rabbits were pretreated i.v. with human IgG (hIgG), i.d. injections of SpA induced an inflammatory response with the classical histologic features of an Arthus reaction. To determine whether this Arthus-like response occurred via a B cell superantigenic mechanism, the rabbits were pretreated with V_H3-depleted hIgG and then were administered SpA i.d. We found that the induction of a prominent inflammatory response by SpA was dependent upon the presence of V_H3⁺ molecules in the hIgG pretreatment. These results provide compelling evidence that an interaction of the B cell SAg, SpA, with its reactive (V_H3⁺) IgGs leads to an immune complex-mediated inflammatory response in vivo.

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