Contribution of FcRn binding to intestinal uptake of IgG in suckling rat pups and human FcRn-transgenic mice

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2013-02, Vol.304 (3), p.G262-G270
• Main Authors: Kliwinski, C, Cooper, P R, Perkinson, R, Mabus, J R, Tam, S H, Wilkinson, T M, Giles-Komar, J, Scallon, B, Powers, G D, Hornby, P J
• Format: Article
• Language: English
• Subjects: Animals; Animals, Suckling - metabolism; Antibodies, Monoclonal - metabolism; Cells; Digestive system; Dose-Response Relationship, Drug; Enterocytes - metabolism; Epithelial Cells - metabolism; Female; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; Humans; Immunoassay; Immunoglobulin G - metabolism; Immunoglobulins; Immunohistochemistry; Intestines - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Monoclonal antibodies; Rats; Receptors, Fc - genetics; Receptors, Fc - metabolism; Rodents; Transcytosis - physiology
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00340.2012

Immunoglobulin G (IgG) is transcytosed across intestinal epithelial cells of suckling mammals by the neonatal Fc receptor (FcRn); however, the contribution of FcRn vs. FcRn-independent uptake to serum IgG levels had not been determined in either rat pups or human (h)FcRn-expressing mice (Tg276 and Tg32). In isoflurane-anesthetized rodents, serum levels were determined after regional intestinal delivery of human monoclonal antibodies (hIgG) with either wild-type (WT) Fc sequences or variants engineered for different FcRn binding affinities. Detection of full-length hIgG was by immunoassay; intestinal hFcRn and hIgG localization was by immunocytochemistry. High (μg/ml) serum levels of hIgG were detected after proximal intestinal delivery (0.1-10 mg/kg) in 2-wk-old rats. Human FcRn was visualized in epithelial cells of Tg276 mice, but low serum hIgG levels (