ReviewPlacental transport of immunoglobulin G
Introduction
If maternal immunization is to protect the newborn, a protective level of specific IgG must be present in the mother’s blood at a time when it can be transferred to the fetus (if the antibody is poorly transported, the maternal level must exceed the protective level). The more specific IgG the fetus receives above the protective level, the longer a protective level will be maintained after birth. The time period in which maternal immunization is effective depends on the timing of the mother’s immune response to the vaccine, and also the timing of maternal–fetal IgG transport. The maternal response is influenced by the vaccine and vaccination protocol and by the mother’s health and immunologic history, and will not be considered here. The timing of the transmission of maternal IgG to the fetus will be discussed. What is known of the mechanism of IgG transport and the limited extent to which this explains its timing will also be considered.
Section snippets
Timing of IgG transport
Two types of study have addressed the development of the capacity to transmit IgG from mother to fetus. Most of the information comes from measurements of the concentrations of endogenous antibodies in maternal and fetal sera at different gestational ages. These include measurements of total IgG, of subclasses of IgG, and of antibodies of particular specificities for antigen. In fewer studies the transport of exogenous antibodies has been measured.
Very little maternofetal transfer of
Subclass differences
The levels of the four subclasses of human IgG in cord blood have been extensively investigated. Particular attention has been paid to IgG2, which is often detected in lower amounts in serum from cord blood than maternal blood, and to IgG1, which is generally found to be more abundant in cord than in maternal samples.
An early study reported cord IgG2 in only trace amounts, in contrast to the other subclasses, which approximately equaled those of the mother in abundance [15]. However, subsequent
Pathway of IgG transport
IgG is transported from mother to fetus across the placenta [1]. During the third trimester, transported IgG crosses the syncytiotrophoblast covering the chorionic villi and the endothelium of fetal capillaries within the villi. These cell layers are separated by their basal laminas, and in some regions by the connective tissue of the stroma (reviewed in [25]).
Syncytiotrophoblast
There is compelling evidence that the MHC class I-related Fc receptor, FcRn, mediates the transmission of IgG across the syncytiotrophoblast. FcRn is expressed in rat and mouse yolk sac [26], [27] and is required for the transmission of IgG from mother to fetus in mice [28]. Despite the differences in placentation, these observations raised the possibility that FcRn might also function in IgG transport to the human fetus. The gene encoding the α chain of mouse FcRn maps to a chromosome region
Concluding remarks
In conclusion, the timing of maternofetal IgG transport in the light of what we know of its mechanism will be considered. During the first trimester of pregnancy, very little IgG is transported to the fetus [5]. IgG is present within the syncytiotrophoblast late in the first trimester [2]. FcRn is expressed in the syncytiotrophoblast by this time [31], and may protect IgG from intracellular degradation. At this stage of development, the syncytiotrophoblast covers a continuous cytotrophoblast
Acknowledgements
This work was supported by NIH grant HD27691.
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