Transfusion of antibody-opsonized red blood cells results in a shift in the immune response from the red blood cell to the antibody in a murine model.

BACKGROUND: It is well known that infusion of immunoglobulin (Ig)G-coated cells results in an inhibited antigen-specific humoral immune response compared to the cells themselves, a phenomenon termed antibody-mediated immune suppression (AMIS). Although this AMIS effect has been well described with many different types of cells as well as vaccines and insoluble antigens, the mechanisms behind this effect remain unresolved. STUDY DESIGN AND METHODS: To study AMIS in a broad context, three different models of AMIS were studied. In the first, mice were transfused with sheep red blood cells (SRBCs) versus IgG-coated SRBCs. In the second, SRBCs expressing the antigen hen egg white lysozyme (HEL) were studied, and the third model consisted of the diphtheria/tetanus vaccine in the absence versus presence of anti-tetanus IgG. The antibody responses to the SRBCs and HEL-SRBCs, as well as the vaccine, were analyzed for up to 4 weeks after challenge. RESULTS: In these mouse models of immunization, the IgG-coated RBCs or HEL-RBCs induced an antibody response against the IgG, rather than against the RBCs. The decreased response to the RBCs was directly related to the increase of the response against the IgG. The inhibitory AMIS effect using the vaccine strategy again showed an immune response against the IgG, concurrent with a decrease in the immune response against the specific vaccine component targeted. CONCLUSIONS: This work demonstrates that, under AMIS conditions, the IgG itself becomes the focus of B cells in the immune system, suggesting a potential mechanism of B-cell regulation.