Studies on the Mechanism by Which Antigen‐Specific IgG Suppresses Primary Antibody Responses: Evidence for Epitope Masking and Decreased Localization of Antigen in the Spleen

Abstract

Immunoglobulin (IgG) has the ability to suppress the Ab response against the Ag to which it binds. Although the mechanism remains unclear, this phenomenon has physiological relevance and is used clinically in Rh prophylaxis. As suppression works well in mice lacking the inhibitory FcgammaRIIB, the two most likely explanations are that IgG masks epitopes and/or that IgG increases the clearance of Ag. In the present study, mice were immunized with sheep red blood cells (SRBC) to which the hapten 5-iodo-4-hydroxyl-3-nitrophenacetyl (NIP) was conjugated at high or low density and the ability of IgG anti-NIP to suppress the Ab response to NIP and SRBC was assayed. Only the NIP-specific response was suppressed when mice were immunized with SRBC-NIP(low), whereas both NIP- and SRBC-specific responses were suppressed when SRBC-NIP(high) was used. This is best explained by epitope masking; at high epitope density, IgG also blocks neighbouring epitopes from recognition by B cells. We also examined the effects of IgG-mediated suppression on T-cell responses directly in vivo. While IgG anti-SRBC administered with sheep red blood cells ovalbumin (SRBC-OVA) almost completely suppressed the anti-SRBC and anti-OVA Ab responses, the OVA-specific T-cell response was still 50% of that observed in control mice. This is probably the result of decreased Ag exposure as IgG-bound SRBC were cleared faster from the bloodstream and were found at lower concentration in the spleen than unbound SRBC. These results suggest that both Ag clearance and epitope masking occurs during IgG-mediated suppression, but that under physiological circumstances epitope masking is the predominant mechanism.