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Mechanisms of Neonatal Mucosal Antibody Protection¹

Nicola L. Harris^2,*,, Iris Spoerri^*, Jacqueline F. Schopfer^*, Chiara Nembrini^*, Patrick Merky^*, Joanna Massacand^*, Joseph F. Urban, Jr., Alain Lamarre, Kurt Burki^*, Bernhard Odermatt^*, Rolf M. Zinkernagel^* and Andrew J. Macpherson^*,¶

^* Institute of Experimental Immunology, Universitätsspital, Zürich, Switzerland; Environmental Biomedicine, Institute of Integrative Biology, Swiss Federal Institute of Technology, Zürich-Schlieren, Switzerland; Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705; Institut National de la Recherche Scientifique-Institut Armand-Frappier, University of Quebec, Laval, Quebec, Canada; and ^¶ Department of Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada

Following an abrupt transition at birth from the sterile uterus to an environment with abundant commensal and pathogenic microbes, neonatal mammals are protected by maternal Abs at mucosal surfaces. We show in mice that different Ab isotypes work in distinct ways to protect the neonatal mucosal surface. Secretory IgA acts to limit penetration of commensal intestinal bacteria through the neonatal intestinal epithelium: an apparently primitive process that does not require diversification of the primary natural Ab repertoire. In contrast, neonatal protection against the exclusively luminal parasite Heligmosomoides polygyrus required IgG from primed females. This immune IgG could either be delivered directly in milk or retrotransported via neonatal Fc receptor from the neonatal serum into the intestinal lumen to exert its protective effect.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ A.J.M. was supported by the Swiss National Science Foundation and Canadian Institutes of Health Research. N.L.H. was supported by a Cancer Research Postdoctoral Fellowship.

² Address correspondence and reprint requests to Dr. Nicola L. Harris, Institute of Integrative Biology, Swiss Federal Institute of Technology, Wagistrasse 27, CH-8952 Zürich-Schlieren, Switzerland. E-mail address: nharris{at}ethz.ch

³ Abbreviations used in this paper: FcRn, neonatal Fc receptor; S-Ig, secretory Ig; ₂m, ₂-microglobulin; SPF, specific pathogen-free; QM, quasimonoclonal.

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