The route of prenatal antibody transmission in both the rat and rabbit is via the yolk sac (Branbell, 1970), and a method for studying in vitro endocytosis in yolk sacs (Williams et al, 1975) was modified as a model for the process of transcellular immunoglobulin transport (Weisbecker, 1981). In this study, the validity of the model was substantiated and various investigations were performed.
The signal mediating specific protection in vitro was shown to reside in the Fc fragment of the IgG molecule, and carbohydrate moieties did not appear to be involved in the interaction.
Neuraminidase-treatment of IgG enhanced protection, while formaldehyde destroyed it. The inference was that the signal sequence was polypeptide in nature, contained a basic amino acid group, and was located close to one of the carbohydrate groups of the molecule, probably the asymmetric, hinge-linked one.
Various inhibitors were shown to inhibit equally uptake into the protective and degradative routes. The evidence suggested a common uptake stage in the uptake of IgG in both pathways.
Release of macromolecular material was found to be sensitive to metabolic inhibitors, but not so much to cytoskeletal ones, EGTA or bulk protein.
In contrast to the hypotheses of Brambell (1966) (where specific membrane-bound receptors are thought sterically to protect IgG from lysosomal degradation) and Wild (1975) (specific micropinocytic coated vesicles carry IgG from the plasmalemma to the basal or lateral membranes), it is proposed that IgG for protection enters common sorting vesicles along with other proteins (mainly destined for degradation) and fluid. It is sorted quickly (before the vesicle becomes too acid) and packaged into specific microvesicles that release their contents at the lateral or basal membranes. It is then free to make its way across the subcellular mesenchyme into the vitelline blood capillaries, and thence into the foetus intact
