Fc gamma RIIB in IgG-mediated suppression of antibody responses: Differentimpact in vivo and in vitro

pression is used clinically in rhesus prophylaxis to prevent RhD-negative m others from becoming immunized against their Ph D-positive fetuses. We have recently,shown that IgG anti-SRBC, passively administered together with SR BC, can induce efficient suppression of primary Ab responses to SRBC in mic e lacking the known FcRs for IgG (Fc gamma RI, Fc gamma III, and Fc gamma R IIB or the neonatal FcR). The lack of a demonstrable effect of the inhibito ry Fc gamma RIIB was particularly surprising, and, in this study, the invol vement 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-defi cient mice. Suppression of secondary Ab responses to SRBC in vivo was simil ar in the two strains. In contrast, IgG-mediated suppression of Ab response s in Nitro was impaired in cultures with primed Fc gamma RIIB-deficient spl een cells. In conclusion, inhibition of in vivo Ab responses to SRBC by pas sively administered IgG can take place via an Fc gamma RIIB-independent pat hway. This pathway causes > 99% suppression and operates during all experim ental 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.