FcγRIIB in IgG-mediated suppression of antibody responses:: Different impact in vivo and in vitro

pression is used clinically in rhesus prophylaxis to prevent RhD-negative mothers from becoming immunized against their Ph D-positive fetuses. We have recently,shown that IgG anti-SRBC, passively administered together with SRBC, can induce efficient suppression of primary Ab responses to SRBC in mice lacking the known FcRs for IgG (Fc gamma RI, Fc gamma III, and Fc gamma RIIB or the neonatal FcR). The lack of a demonstrable effect of the inhibitory Fc gamma RIIB was particularly surprising, and, in this study, the involvement of this receptor is further investigated during broader experimental conditions. The data show that SRBC-specific IgG administered up to 5 days after SRBC can induce suppression both in wild-type and Fc gamma RIIB-deficient mice. Suppression of secondary Ab responses to SRBC in vivo was similar in the two strains. In contrast, IgG-mediated suppression of Ab responses in Nitro was impaired in cultures with primed Fc gamma RIIB-deficient spleen cells. In conclusion, inhibition of in vivo Ab responses to SRBC by passively administered IgG can take place via an Fc gamma RIIB-independent pathway. This pathway causes > 99% suppression and operates during all experimental conditions studied so far. The nature of the mechanism can at present only be hypothesized. Masking of epitopes and/or rapid elimination of IgG-Ag complexes would both be compatible with the observations.