Maternal IgG transfer across placenta represents transfer of ready-made immunity from mother to fetus, a form of. After all, it takes one or two years for B cells of human newborns to secrete adult level antibodies.
Antibodies (immunoglobulins) are secreted versions of the(BCR) of the . Through a process called class switch recombination (CSR) or , ‘help’ enables B cells to switch from native IgM to other antibody such as IgGs (IgG1, 2, 3, 4), IgA, IgE.
and IgA are the most abundant and apparently the most consequential since their absence confers serious susceptibility to infections. Given its importance and effectiveness in blocking infections in general, mammals and other classes such as birds and even fishes appear to have evolved a variety of methods to transfer IgG from mother to fetus either antenatally through the placenta or postnatally through colostrum and breastmilk.
Maternal IgG Is Transmitted To Fetus Only In Species With Hemochorial Placenta
Important to recall here the wide variety of placental design in different mammals, with the most invasive form of placenta, the hemochorial, found in higher order primates such as humans, rodents such as mice, rats, guinea pigs, and lagomorphs such as rabbits, where placentalcells are in direct contact with maternal blood (see below from 1).
Wide variety of mother-to-fetus IgG transfer (2, 3) reflects this wide placental design. IgG isn’t transplacentally transported in all mammalian species but rather is a feature of hemochorial placenta. However, even hemochorial placenta does not automatically mean transplacental IgG transfer.
Maternal IgG persists for different lengths of time in different species, as short as 10 days in some fishes to as long as ~9 months in humans. See below from 4 a summation of the variety of ways by which maternal IgGs are transmitted from mother to fetus or newborn, the varying lengths of time such antibodies can persist after transfer and the wide range of species they protect from disease.
- In humans, rats, mice, maternal antibodies are transferred both pre- (IgG, see below from ) and post-natally (IgA, little IgG).
- In rabbits and guinea pigs, maternal antibodies are transferred only pre-natally.
- In ungulates (ruminants, horses, pigs), there is no pre-natal maternal antibody transmission. Rather, bolus amounts of maternal antibody, largely IgG, pass from mother to newborn through colostrum in the 36 to 48 hours post-birth.
, considered the father of the field of transmission of immunity (3),
- Generated the first modern data to describe transfer of antibodies from mother to fetus via placenta with a 1949 rabbit study ( ).
- Defined the first system for IgG.
- Identified the link necessary between mother-to-fetus transfer of IgG and need to protect the IgG molecule from catabolism.
Regardless it is transmitted from mother to fetus through placenta or through milk, in order for maternal IgG or any other type of antibody to be of any immunological usefulness to fetus and neonate, it has to reach the circulation intact after traversing complicated biological barriers such as trophoblast cells and fetal or newborn capillaries. Brambell predicted a unique transport system must exist to transport maternal IgG intact across placenta (human) or newborn GI tract (rodent) and into its bloodstream, a prediction proven years later by the discovery of the(FcRn), also called the Brambell factor (see below from the visualization of how FcRn transports IgG across GI tract and placenta).
History of Maternal Transmission of Immunoglobulins, Specifically of IgG
Starting in the 1870s, data started accumulating to suggest transplacental IgG antibody transfer is important for infant immunity.
- Studies published in 1877 and 1880 observed that lambs born to ewes recently vaccinated against cowpox (7) and anthrax (8) were also protected against them.
in 1892 (9) and in 1893 (10) showed that transfer of maternal immunity from mother to offspring was important for newborn health.
- Ehrlich’s observations were crucial and groundbreaking because the experiments were brilliantly conceived to link transfer and outcome.
- Baby mice born to mothers made immune to toxins were also immune, and though such immunity was limited in time, it could be extended if baby mice suckled immune mothers but not non-immune wet nurses.
- Something specific clearly needed to pass from mother to fetus in utero and in milk that endowed babies with immune resistance to toxins.
- In short order followed reports that mothers transferred protective factors, now known to be antibodies, that protected guinea pigs (11, ) and humans (13, 14) against diphtheria and tetanus.
See below fromthe wide range of species maternal antibodies, mainly IgGs, protect from disease.
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2. Kristoffersen, Einar Klæboe. “Human placental Fcγ‐binding proteins in the maternofetal transfer of IgG.” Apmis 104.S64 (1996): 5-36.
3. Junghans, R. P. “Finally! The Brambell receptor (FcRB).” Immunologic research 16.1 (1997): 29-57.
4. Grindstaff, Jennifer L., Edmund D. Brodie, and Ellen D. Ketterson. “Immune function across generations: integrating mechanism and evolutionary process in maternal antibody transmission.” Proceedings of the Royal Society of London B: Biological Sciences 270.1531 (2003): 2309-2319.
5. Brambell, F. W., et al. “The passage into the embryonic yolk‐sac cavity of maternal plasma proteins in rabbits.” The Journal of physiology 108.2 (1949): 177-185.
6. Roopenian, Derry C., and Shreeram Akilesh. “FcRn: the neonatal Fc receptor comes of age.” Nature reviews. Immunology 7.9 (2007): 715.
7. Bollinger, Otto. Über Menschen-und Thierpocken, über den Ursprung der Kuhpocken und über intrauterine Vaccination. Breitkopf & Härtel, 1877.
8. Chauveau, A. “Du renforcement de l’immunite des moutons algeriens a l’egard du sang de rate, par les inoculations preventives.” CR Acad. Sci.(Paris) 91 (1880): 148-151.
9. Ehrlich, Paul. “Über immunität durch vererbung und säugung.” Medical Microbiology and Immunology 12.1 (1892): 183-203.; Ehrlich, Paul, and W. Hübener. “Über die Vererbung der Immunität bei Tetanus.” Medical Microbiology and Immunology 18.1 (1894): 51-64.
10. Klemperer, Felix. “Ueber natürliche Immunität und ihre Verwerthung für die Immunisirungstherapie.” Archiv für Experimentelle Pathologie und Pharmakologie 31.4-5 (1893): 356-382.
11. Wernicke, E. “Über die Vererbung der künstlich erzgeuten Diphtherie-Immunität bei Meerschweinen.” Festschrift zur 100 (1895).
12. Smith, Theobald. “Degrees of susceptibility to diphtheria toxin among guinea-pigs. Transmission from parents to offspring.” The Journal of medical research 13.3 (1905): 341.
13. Fischl, Rudolf, and Gustav von Wunschheim. Über Schutzkörper im Blute des Neugeborenen: das Verhalten des Blutserums des Neugeborenen gegen Diphtheriebacillen und Diphtheriegift: nebst kritischen Bemerkungen zur humoralen Immunitätstheorie.
14. Polano, O. “Der Antitoxinübergang von der Mutter auf das Kind: Ein Beitrag zur Physiologie der Placenta.” Ztschr. f. Geburtsh. u. Gynäk. 53 (1904): 456.