IN-VIVO INFLAMMATORY RESPONSE TO A PROTOTYPIC B-CELL SUPERANTIGEN - ELICITATION OF AN ARTHUS REACTION BY STAPHYLOCOCCAL PROTEIN-A

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 complementary- determining regions, In addition, B cell SAgs can react with a substan tial amount of a host's serum Igs by virtue of their ability to intera ct with many members of an entire variable heavy chain (V-H) or variab le light chain gene family. For example, SpA reacts with the Fabs of m ost human Igs using heavy chains from the V(H)3 gene family (V(H)3(+)) . Members of this gene family are expressed on 30 to 60% of human peri pheral B cells. We sought to determine whether the interaction of a B cell SAg with its reactive Igs can elicit immune complex-mediated tiss ue injury. Using the Arthus reaction in rabbits as an in vivo model of immune complex-mediated tissue inflammation, me demonstrated that unt reated rabbits, which were administered SpA intradermally (i.d.), do n ot develop a cutaneous inflammatory response. However, when rabbits me re pretreated i.v. with human IgG (hIgG), i.d. injections of SpA induc ed an inflammatory response with the classical histologic features of an Arthus reaction, To determine whether this Arthus-like response occ urred via a B cell superantigenic mechanism, the rabbits were pretreat ed with V(H)3-depleted hIgG and then mere administered Spa i.d. We fou nd that the induction of a prominent inflammatory response by SpA was dependent upon the presence of V(H)3(+) molecules in the hIgG pretreat ment. These results provide compelling evidence that an interaction of the B cell SAg, SpA, with its reactive (V(H)3(+)) IgGs leads to an im mune complex-mediated inflammatory response in vivo.