The brahbell protection receptor (FcRp) for IgG catabolism is the neo-natal intestinal transport receptor ( FcRn )

More than 30 years aao. Brambell postulated that the long survival of IgG is mediated by specific "protection receptor" (PcRp) that bind IgG in pinocytic vacuoles and redirect it to the circulation, thus escaping lys- \ osomal catabolism. Brambell similarly t described the neonatal gut transport j receptor (FcRn). The FcRn wae recently cloned, but the FcRp has not been identified, using a genetic knockout that disrupts the FcRn and intestinal IgG transport, we show that this lesion also disrupts the IgG protection receptor, supporting the identity of these two receptors. IgG catabolism was 10-fold faster and IgG levels correspondingly lower in mutant than in wildtype mice, whereas IgA and IgM were similar between groups, reflecting the specific effects on the IgG system. Disruption of the FcRp also abrogated the classical pattern of decreased IgG survival with higher IgG concentration. Studies with monomeric complexes showed that antigen bound to antibody in normal mice recycled through the endosome three times before it dissociated and passed to the lysosome for catabolism versus eight times (2x per day) for antibody.