Presentation of antigen in immune complexes is boosted by soluble bacterial immunoglobulin binding proteins

Using a snake toxin as a proteic antigen (Ag), two murine toxin-specific mo noclonal antibodies (mAbs), splenocytes, and two murine Ag-specific T cell hybridomas, we showed that soluble protein A (SpA) from Staphylococcus aure us and protein G from Streptococcus subspecies, two Ig binding proteins (IB Ps), not only abolish the capacity of the mAbs to decrease Ag presentation but also increase Ag presentation 20-100-fold. Five lines of evidence sugge st that this phenomenon results from binding of an IBP-Ab-Ag complex to B c ells possessing IBP receptors. First, we showed that SpA is likely to boost presentation of a free mAb, suggesting that the IBP-boosted presentation o f an Ag in an immune complex results from the binding of IBP to the mAb. Se cond, FACS(R) analyses showed that an Ag-Ab complex is preferentially targe ted by SpA to a subpopulation of splenocytes mainly composed of B cells. Th ird, SpA-dependent boosted presentation of an Ag-Ab complex is further enha nced when splenocytes are enriched in cells containing SpA receptors. Fourt h, the boosting effect largely diminishes when splenocytes are depleted of cells containing SpA receptors. Fifth, the boosting effect occurs only when IBP simultaneously contains a Fab and an Fc binding site. Altogether, our data suggest that soluble IBPs can bridge immune complexes to APCs containi ng IBP receptors, raising the possibility that during an infection process by bacteria secreting these IBPs, Ag-specific T cells may activate IBP rece ptor-containing B cells by a mechanism of intermolecular help, thus leading to a nonspecific immune response.