Identification and function of neonatal Fc receptor in mammary gland of lactating mice

Abstract

In addition to its proposed function in regulating serum IgG levels, the MHC class I‐related neonatal Fc receptor (FcRn) is known to play a role in IgG transfer across rodent yolk sac and neonatal intestine. In contrast to humans, for which transplacental transfer of IgG appears to be the only mechanism of maternal IgG delivery, the transmission of IgG in mice occurs both antenatally (yolk sac) and neonatally (transport from mother's milk across intestinal epithelial cells). In the current study, a possible role for FcRn in regulating IgG transfer into milk has been investigated. FcRn has been shown to be present in functional form in the mammary gland of lactating mice, and is localized to the epithelial cells of the acini. Analysis of the transfer of Fc fragments and IgG which have different affinities for FcRn indicate that, unexpectedly, these proteins are transferred in inverse correlation with their binding affinity for FcRn. Thus, in the lactating mammary gland FcRn appears to play a role in recycling IgG in a mode that may have relevance to FcRn trafficking during the maintenance of constant serum IgG levels.

Accelerating antibody discovery using transgenic animals overexpressing the neonatal Fc receptor as a result of augmented humoral immunity

“…Altogether, the data suggested that bFcRn could bind both mouse and hIgGs, showing a crossspecies FcRn-IgG binding activity. However, we found no selective accumulation of endogenous mIgG or injected bovine IgG (bIgG) in the milk of Tg females (23), supporting a previous hypothesis that the role of FcRn in the mammary gland is to recycle IgG from this tissue to the blood instead of secreting it to the milk (24). In agreement with this observation, a recent study indicated that the bFcRn binds better to bIgG2 than bIgG1 (six-to sevenfold difference in K d ) and thus we concluded that the role of bFcRn is to recycle IgG2 from the udder to blood instead of secreting it from blood to colostrum/milk, as in mice and humans (22,(24)(25)(26).…”

Mother to Child Transfer of IgG and IgA Antibodies Against Dermatophagoides pteronyssinus

“…The latter mechanism may operate in the atopic group because there was no correlation between maternal serum and colostrum Der pspecific IgG levels in that group. Studies in rodents suggest that, as in the placenta, FcRn can be involved in IgG transfer across mammary gland epithelium [55]. Notably, in contrast to IgA that stays in the gut lumen, anti-Der p IgG can then be transferred to the neonate by FcRn expressed in the human proximal intestine [39,56].…”

Androgen‐dependent expression of FcγRIIB2 by thyrocytes from patients with autoimmune Graves' disease: a possible molecular clue for sex dependence of autoimmune disease

“…Although FcRn can transcytose in the basolateral to apical or, conversely, in the apical to basolateral directions (20) in vivo, the net transport of IgG has so far been observed only in the lumenal to the serosal direction (27). In liver, kidney, and mammary glands, FcRn is in contact with IgG on the serosal side but it does not transfer IgG to the lumen, suggesting that in these tissues the function of FcRn is restricted to the recycling of IgG (30). However, FcRn-mediated basolateral to apical transport of aAb in thyrocytes can not a priori be excluded since the intracellular transport of proteins in thyrocytes can differ from that in others epithelial cells (31).…”