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RIIB in IgG-Mediated Suppression of Antibody Responses: Different Impact In Vivo and In Vitro1
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
The suppressive effect of IgG on Ab responses to particulate Ags
such as erythrocytes is well documented. IgG-mediated suppression is
used clinically in rhesus prophylaxis to prevent RhD-negative mothers
from becoming immunized against their Rh 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
RI, FcIII, and
FcRIIB or the neonatal FcR). The lack of a demonstrable effect of
the inhibitory FcRIIB 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 FcRIIB-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 vitro was impaired in
cultures with primed FcRIIB-deficient spleen cells. In conclusion,
inhibition of in vivo Ab responses to SRBC by passively administered
IgG can take place via an FcRIIB-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.
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