The novel mechanism for transporting antibodies centers on a cellular transporter - FcRn - better known for transporting antibodies from a mother's milk into the bloodstream of an infant to provide immune protection during the first few days of life.

The role of IgG in cellular secretions has not been studied much, says Richard S. Blumberg of Harvard Medical School in Boston, but people with aberrations in IgG are very sick, he said, with intestinal and lung problems. "Now we have an explanation for how IgG gets into secretions."

One reason why there has been little work on the transport of IgG is because the FcRn shuttle is only present in young and not in adult rodents, says Blumberg. Recently, however, his lab showed that the FcRn receptor is present in the intestinal epithelial cells of adult humans, as well as in the dendritic cells and intestinal macrophages of the immune system.

One logical interpretation of these data, according to Blumberg, is that adult FcRn might play a role in the uptake of antibodies and antigens bound to antibodies from the intestinal and/or other mucosal surfaces. These immune complexes could influence subepithelial B- and T-cell responses, he says, and have a role in immune tolerance, whereby immune cells do not react to the body's own cells or common antigens, such as those found in food.

Using a line of canine kidney cells, a common model of epithelial cells, Blumberg and his colleagues demonstrated that FcRn could transport IgG from the apical to the basal surface of cells. Specific antigens that reacted with the IgG could also be transported as complexes. "There was clear transport of immune complexes in the presence of a specific antibody but not in the absence of a specific antibody or in the absence of FcRn," he said.

This transport system is also functional in transgenic mice expressing both human FcRn and a protein, β₂m, which is required to make functional FcRn. A fluorescently labelled albumin-antibody complex injected into these transgenic mouse was soon found lining the intestine, says Blumberg.

Two hours later, the fluorescing complexes had been transported into the endothelial cells along the intestine, and within three hours, up to 10% of dendritic cells were expressing the signal. In mice lacking FcRn, there was no evidence that the fluorescent complexes had moved from the lumen of the intestine, said Blumberg, suggesting that FcRn was the key transporter.

All this suggests that FcRn is a third system that takes antigens from the intestinal lumen and exposes them to dendritic cells. "All of these pathways play a very important role in maintaining oral tolerance," said Blumberg.

"This is very novel research, and quite interesting," said Jerry R. McGhee of the University of Alabama at Birmingham, who chaired the symposium on mucosal immunity. "We know a lot about secretory IgA, but IgG has been ignored because we didn't know how it got to the lumen." Blumberg's work should stimulate much more research in the field, said McGhee.