Over‐expression of the bovine FcRn in the mammary gland results in increased IgG levels in both milk and serum of transgenic mice

Abstract

SummaryThe neonatal Fc receptor (FcRn) protects immunoglobulin G (IgG) from catabolism and is also responsible for IgG absorption in the neonatal small intestine. However, whether it mediates the transfer of IgG from plasma to milk still remains speculative. In the present study, we have generated transgenic mice that over-express the bovine FcRn (bFcRn) in their lactating mammary glands. Significantly increased IgG levels were observed in the sera and milk from transgenic animals, suggesting that the over-expressed bFcRn could bind and protect endogenous mouse IgG and thus extend its lifespan. We also found that injected human IgG showed a significantly longer half-life (7-8 days) in the transgenic mice than in controls (2Á9 days). Altogether, the data suggested that bFcRn could bind both mouse and human IgG, showing a cross-species FcRnIgG binding activity. However, we found no selective accumulation of endogenous mouse IgG or injected bovine IgG in the milk of the transgenic females, supporting a previous hypothesis that IgG was transported from serum to milk in an inverse correlation to its binding affinity to FcRn.

Neonatal FcR Expression in Bone Marrow-Derived Cells Functions to Protect Serum IgG from Catabolism

“…Although it is difficult to ascribe exactly the contribution of the hemopoietic cell population to IgG homeostasis, the bone marrow chimera experiments demonstrate that it plays a significant role, at a level that is potentially similar to the role of endothelial cells. FcRn expressed at other sites may also extend the half-life of serum IgG as suggested for FcRn expressed in the mammary gland (45). Taken together, however, our results suggested that bone marrow-derived cells and vascular endothelial cells are major cell types responsible for the FcRn-dependent extension of serum IgG half-life.…”

Neonatal FcR Overexpression Boosts Humoral Immune Response in Transgenic Mice

“…Increasing the FcRn expression by transgenesis to reduce IgG clearance is yet an unexplored approach for improving hyperimmunization. We and others have recently shown that higher than normal expressional level of FcRn reduced exogenous IgG catabolism (11,14,34).…”

“…The mechanism was originally thought to be mediated mainly by endothelial cells, which line blood vessels (8). However, recent findings suggest that this process occurs also in hematopoietic cells (9,10), or even in mammary epithelial cells during lactation (11).…”

The Fate and Function of Therapeutic Antiaddiction Monoclonal Antibodies across the Reproductive Cycle of Rats

“…The development of the mammary glands and deposition/accumulation of IgG in colostrum late in pregnancy (Lu et al, 2007) could also represent an extravascular sink for IgG, possibly contributing to the observed third trimester and postpartum V d changes (Table 2). It is noteworthy that these hemodynamic changes in the rat model could mimic human changes (Dowell and Kauer, 1997), suggesting that mAb V d and Cls changes may also occur during human pregnancy.…”