With its expression as a heterodimer of a glycosylated heavy chain associated with 2microglobulin, our laboratory has previously provided evidence for a possible protective role for the FcRn by establishing an increased catabolism of IgG seen in 2microglobulin-deficient mice (12). from human fetal intestine and from a nonmalignant human fetal intestinal epithelial cell line (H4) were subjected to Western blot analysis and probed using anti-FcRn antibodies. A 42-kD band, consistent with the known molecular weight of the FcRn, was detected along the human fetal intestine and in H4 cells. Expression of the human FcRn was confirmed with immunohistochemistry. Our study demonstrates the expression of FcRn along the human fetal intestine and in a human nonmalignant fetal intestinal epithelial cell line (H4), which by location indicates that FcRn could play a role in the uptake and transport of IgG in the human fetus. Humoral immunity acquiredviamaternofetal transfer of antibody is critical in the prevention of perinatal infections. In rodents, this transfer occurs through the yolk sac and the intestineviaa Fc receptor for IgG (FcRn). This receptor has been considered important in the maternofetal transmission of IgG in the yolk sac of mice and rats and also in the human placental syncytiotrophoblast (1). The FcRn is also expressed in the small intestine of suckling mice and rats, where the receptor functions in the uptake of IgG from ingested maternal milk. Although a FcRn has been demonstrated around the human fetal small intestine, a similar function for this receptor in the human fetal intestine has not been demonstrated to date. The acquisition of humoral immunity early in life may have a significant lifelong impact on the prevention of infectious and inflammatory diseases. Because IgG synthesis in the human fetus is reduced, most IgG in MTC1 the blood of newborns is usually maternal in origin. Low levels of IgG have been detected in the plasma of 12-wk-old fetuses, with levels reaching maternal concentrations by 26 wk of gestation. This rise in serum IgG in the fetus occurs in parallel with the rise in IgG in amniotic fluid, with highest concentrations reached between 15 and 33 wk, around the time when the fetus begins to swallow (2,3). Because the major placental transfer of IgGviathe FcRn occurs after 22 wk, it is possible that an earlier transfer from swallowed amniotic fluid may occurviathe fetal intestine (2,3). Although an Fc binding site has been identified in the human small intestine (3) with a structure that seems to be identical to the cloned human syncytiotrophoblast Fc receptor (1), the distribution of this receptor throughout the fetal intestine has not been clearly defined. Accordingly, the aim of this study was to further characterize the expression of the FcRn in human fetal intestine as a prelude to determining its role in the protective function of maternal IgG in the newborn. Using human fetal intestinal models established in this laboratory, we sought to characterize the distribution of the FcRn along the human fetal intestine. == MATERIALS AND METHODS == == Human cell lines == Caco2 and T84 cell lines were used to represent human intestinal epithelial cells. The H4 cell line is a primary nonmalignant fetal small intestinal epithelial cell line that has been characterized in our laboratory (4). It was used as a model for fetal enterocytes. Cell passages of H4 cells from 20 to 34 were studied. H4 cells were produced in Dulbeccos modified Eagles medium (DMEM; GIBCO, Grand Island, NY, U.S.A.) supplemented with 5% fetal bovine serum (FBS) (BioWhittaker, UPGL00004 Walkersville, MD, U.S.A.), 2 mM glutamine (GIBCO), 100,000 U/L penicillin, and 100 mg/L streptomycin (GIBCO). The Caco2 cell line was purchased from the American Type Culture Collection (Manassas, VA, U.S.A.). Caco2 cells were produced in 10% FBS, 2 mM glutamine, 0.1 mM nonessential amino acids, 100,000 U/L penicillin, 100 mg/L streptomycin, and 10 mM HEPES UPGL00004 buffer solution under a humidified atmosphere at 37C and 5% CO2. T84 cells were generously provided by Dr. Beth McCormick of the Mucosal Immunology Laboratory at Massachusetts General Hospital East, Charlestown, MA. T84 cells were grown in media made up of DMEM withl-glutamine, Hams F12 Nutrient mixture withl-glutamine, 0.014 UPGL00004 M sodium bicarbonate, 0.015 MN-2-hydroxyethylpiperazine-N’-2-ethanesulfonic acid (HEPES) buffer solution, 0.04 g/L penicillin, 0.09g/L streptomycin, and 10% FCS. == Human intestinal tissue == All human tissue was used after obtaining informed consent according to the regulations of the Human Studies Committee at the Brigham and Womens Hospital and Massachusetts General Hospital, Boston. Human fetal intestine was derived from aborted fetuses, aged 1822 wk. Fetal gastrointestinal.