Elsevier

Vaccine

Volume 21, Issue 24, 28 July 2003, Pages 3365-3369
Vaccine

Review
Placental transport of immunoglobulin G

https://doi.org/10.1016/S0264-410X(03)00334-7Get rights and content

Abstract

Maternal antibodies transported across the placenta protect the newborn. Maternal immunoglobulin G (IgG) concentrations in fetal blood increase from early in the second trimester through term, most antibodies being acquired during the third trimester. IgG1 is the most efficiently transported subclass and IgG2 the least. Transfer across the syncytiotrophoblast of the chorionic villi is mediated by the neonatal Fc receptor, FcRn. Immune complexes are absorbed in the stroma of the villi, probably by FcγRI, FcγRII, and FcγRIII on placental macrophages. The mechanism of IgG transport across the endothelium of fetal capillaries is not understood. Endothelial cells in terminal villi express FcγRIIb. However, it is not known whether this receptor transports IgG or prevents transport of immune complexes to the fetus.

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.

References (76)

  • N.E. Simister

    Human placental Fc receptors and the trapping of immune complexes

    Vaccine

    (1998)
  • T. Kameda et al.

    Localization of three subtypes of Fcγ receptors in human placenta by immunohistochemical analysis

    Placenta

    (1991)
  • S.P. Karas et al.

    Characterization of the IgG-Fc receptor on human platelets

    Blood

    (1982)
  • P.T. Harrison et al.

    Binding of monomeric immunoglobulin G triggers Fc gamma RI-mediated endocytosis

    J. Biol. Chem.

    (1994)
  • J.A. Firth et al.

    Not trophoblast alone: a review of the contribution of the fetal microvasculature to transplacental exchange

    Placenta

    (1996)
  • R.A. Simpson et al.

    From 13 weeks to term, the trophoblast of human placenta grows by the continuous recruitment of new proliferative units: a study of nuclear number using the disector

    Placenta

    (1992)
  • M. Koyama et al.

    Differential mRNA expression of three distinct classes of Fc gamma receptor at the feto-maternal interface

    J. Reprod. Immunol.

    (1991)
  • N.A. Bright et al.

    Cytotrophoblast cells: a barrier to maternofetal transmission of passive immunity

    J. Histochem. Cytochem.

    (1995)
  • P. Linnet-Jepsen et al.

    On the inheritance of the gm serum group

    Acta Genet.

    (1958)
  • D. Gitlin et al.

    Serum alpha-fetoprotein, albumin, and gamma-globulin in the human conceptus

    J. Clin. Invest.

    (1966)
  • D. Gitlin et al.

    Development of γg, γa, γm, ßic/ßia, c′1 esterase inhibitor, ceruloplasmin, transferrin, hemopexin, haptoglobin, fibrinogen, plasminogen, α1-antitrypsin, orosomucoid, ß-lipoprotein, α2-macroglobulin, and prealbumin in the human conceptus

    J. Clin. Invest.

    (1969)
  • A. Morell et al.

    Correlations between the concentrations of the four sub-classes of IgG and gm allotypes in normal human sera

    J. Immunol.

    (1972)
  • B.Z. Garty et al.

    Placental transfer of immunoglobulin G subclasses

    Clin. Diagn. Lab. Immunol.

    (1994)
  • A. Malek et al.

    Evolution of maternofetal transport of immunoglobulins during human pregnancy

    Am. J. Reprod. Immunol.

    (1996)
  • A. Morell et al.

    Human IgG subclasses in maternal and fetal serum

    Vox Sang

    (1971)
  • A. Malek et al.

    Maternal–fetal transport of immunoglobulin G and its subclasses during the third trimester of human pregnancy

    Am. J. Reprod. Immunol.

    (1994)
  • L.G. Longsworth et al.

    The electrophoretic analysis of maternal and fetal plasmas and sera

    J. Clin. Invest.

    (1945)
  • P.F. Kohler et al.

    Elevation of cord over maternal IgG immunoglobulin: evidence for an active placental IgG transport

    Nature

    (1966)
  • F.C. Hay et al.

    The transfer of human IgG subclasses from mother to foetus

    Clin. Exp. Immunol.

    (1971)
  • A.C. Wang et al.

    Chemical differences of adult, fetal and hypogammaglobulinemic IgG immunoglobulins

    Immunochemistry

    (1970)
  • Chandra RK. Levels of IgG subclasses, IgA, IgM, and tetanus antitoxin in paired maternal and foetal sera: findings in...
  • Catty D, Drew R, Seger R. Transmission of IgG subclasses to the human fetus. In: Hemmings WA, editor. Protein...
  • G. Virella et al.

    Placental transfer of human IgG subclasses

    Clin. Exp. Immunol.

    (1972)
  • O.J. Mellbye et al.

    Presence and origin of human IgG subclass proteins in newborns

    Vox Sang

    (1973)
  • R.W. Pitcher-Wilmott et al.

    The placental transfer of IgG subclasses in human pregnancy

    Clin. Exp. Immunol.

    (1980)
  • Yeung CY, Hobbs JR. Serum gamma-globulin levels in normal premature, post-mature, and “small-for-dates” newborn babies....
  • Kaufmann P, Burton G. Anatomy and genesis of the placenta. In: Knobil E, Neill JD, editors. The physiology of...
  • D.M. Roberts et al.

    Isolation and characterization of the Fc receptor from the fetal yolk sac of the rat

    J. Cell. Biol.

    (1990)
  • Cited by (622)

    View all citing articles on Scopus
    View full text