Dr. Anderson studies the function of an important transporter molecule of the immune system. FcRn is an intracellular membrane glycoprotein heterodimer, largely intracellular, consisting of beta2-microglobulin and an alpha-chain of the nonclassical MHC1 family of molecules. A receptor for both albumin and IgG, it expresses independent high affinity binding sites for both ligands at acidic pH but not at physiologic pH.

FcRn has essentially three functions. Situated in acidic vesicles of virtually all cells of the body FcRn binds IgG and albumin that have been nonspecifically endocytosed, and exocytoses both molecules to the pH-neutral exterior of the cell so they can continue to circulate in the milieu of the tissue, diverting both molecules thereby from a degradative lysosomal fate. This specific salvaging process, driven by a pH gradient, causes both albumin and IgG to have uniquely lengthy half-lives and to show a uniquely inverse relationship between their serum concentration and half-life. The recycling process has extraordinary capacity. Had we failed to evolve an FcRn, we would require two livers the size of our existing liver to keep our albumin concentration normal, and we would need to biosynthesize four times more IgG than we do.

The second function is to transport both albumin and IgG back and forth across the microvascular endothelium of the body. Our studies indicate that a large fraction of the total flux of both ligands is due to the action of FcRn.

Third, FcRn is the molecule responsible for the transport of IgG from maternal circulation to the circulation of the immunologically immature offspring, providing the fetus and newborn with mother’s full complement of protective IgG antibodies. Of the two cell layers that separate mother from young, the first expresses FcRn. How IgG crosses the second layer is not known although we have found a second FcR expressed in this layer, FcγRIIb2, a member of the family of classical FcγR, completely different from FcRn. Whether FcγRIIb2 transports IgG we are studying. Whether and how albumin might traverse from mother to young is also an exciting rekindled question.

Focusing on these fundamental questions, Dr. Anderson’s lab utilizes all necessary resources and methods from the disciplines of immunology, cell and molecular biology, and biochemistry.