Regulation of antibody responses via antibodies, complement, and Fc receptors

Abstract

Antibodies can completely suppress or enhance the antibody response to their specific antigen by several hundredfold. Immunoglobulin M (IgM) enhances antibody responses via the complement system, and complement activation by IgM probably starts the chain of events leading to antibody responses to suboptimal antigen doses. IgG can enhance primary antibody responses in the absence of the complement system and seems to be dependent on Fc receptors for IgG (FcgammaRs). IgE enhances antibody responses via the low-affinity receptor for IgE (FcepsilonRII/CD23). The precise effector mechanisms that cause enhancement are not known, but direct B-cell signaling, antigen presentation, and increased follicular localization are all possibilities. IgG, IgE, and IgM may also suppress antibody responses when used in certain immunization regimes, and it seems reasonable that an important mechanism behind suppression is the masking of antigenic epitopes by antibodies. In addition, FcgammaRIIB, which contains a cytoplasmic inhibitory motif, acts as a negative regulator of antibody responses. This receptor, however, may prevent the antibody responses from exceeding a certain level rather than causing complete suppression.