MINISYMPOSIUM IX. Immune Mechanisms in Pregnancy: Antibodies, Complement, and Cytokines.
11:00 AM-12:30 PM
Harborside A & B
Chair: Hunt, Joan 1, 1
(M26) IgG TRANSPORT ACROSS THE HUMAN PLACENTA.
Anderson, Clark1, 1 Department of Internal Medicine, Columbus, OH
ABSTRACT- Antibody is transported across the human placenta from maternal circulation to the fetus so that the infant benefits from its mothers full complement of protective IgG antibodies while its own immune system matures. IgG must broach two cell barriers, the syncytiotrophoblast and the placental endothelium. The hypothesis describing transport across the former cell barrier states that IgG is pinocytosed nonspecifically along with other serum proteins and moves to an acidic intracellular compartment where it encounters FcRn, the MHC-related Fc receptor that binds IgG with high affinity at low pH but shows no affinity at physiologic pH. FcRn effectively diverts IgG from a degradative fate in lysosomes suffered by most other proteins, instead transporting it across to the basolateral surface, where, under the influence of neutral pH, it dissociates from the receptor and is free then to move to the endothelial layer. This very same mechanism appears to be used in other cells of the body throughout the life of the individual to protect IgG from degradation, thus prolonging its lifespan to a period far greater than most proteins not so protected. Although much remains to be learned about this transport mechanism, the broad outline is clear. The receptor in complex with its ligand have been crystalized; the mechanism of interaction has been analyzed in great detail; and the expression of this mechanism throughout the animal kingdom is apparent. Once across the syncytiotrophoblast, IgG must then traverse the placental endothelium before reaching the fetal circulation. Considerably less is known about how this occurs. Although it is conceivable that this occurs passively, we have recently shown that another Fc receptor, not at all related to FcRn, is expressed in placental endothelium and not in any other endothelium of the body. There appears to be no other function that would explain its presence. This is FcgRIIb, a single chain glycoprotein of 43 kDa. FcgRIIb is characterized by a distinctive tyrosine-centered signaling motif in its cytoplasmic tail that attracts a variety of signal transduction molecules and is central to regulation of the response of lymphocytes and macrophages to IgG immune complexes. The enticing conjecture that FcgRIIb serves to transport IgG across placental endothelium has a variety of testable predictions.
KEY WORDS: IgG, antibody, transport, FcRn