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Characterization of the Rabbit Neonatal Fc Receptor (FcRn) and Analyzing the Immunophenotype of the Transgenic Rabbits That Overexpresses FcRn

The neonatal Fc receptor (FcRn) regulates IgG and albumin homeostasis, mediates maternal IgG transport, takes an active role in phagocytosis, and delivers antigen for presentation. We have previously shown that overexpression of FcRn in transgenic mice significantly improves the humoral immune respo...

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Autores principales: Catunda Lemos, Ana Paula, Cervenak, Judit, Bender, Balázs, Hoffmann, Orsolya Ivett, Baranyi, Mária, Kerekes, Andrea, Farkas, Anita, Bősze, Zsuzsanna, Hiripi, László, Kacskovics, Imre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256154/
https://www.ncbi.nlm.nih.gov/pubmed/22247762
http://dx.doi.org/10.1371/journal.pone.0028869
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author Catunda Lemos, Ana Paula
Cervenak, Judit
Bender, Balázs
Hoffmann, Orsolya Ivett
Baranyi, Mária
Kerekes, Andrea
Farkas, Anita
Bősze, Zsuzsanna
Hiripi, László
Kacskovics, Imre
author_facet Catunda Lemos, Ana Paula
Cervenak, Judit
Bender, Balázs
Hoffmann, Orsolya Ivett
Baranyi, Mária
Kerekes, Andrea
Farkas, Anita
Bősze, Zsuzsanna
Hiripi, László
Kacskovics, Imre
author_sort Catunda Lemos, Ana Paula
collection PubMed
description The neonatal Fc receptor (FcRn) regulates IgG and albumin homeostasis, mediates maternal IgG transport, takes an active role in phagocytosis, and delivers antigen for presentation. We have previously shown that overexpression of FcRn in transgenic mice significantly improves the humoral immune response. Because rabbits are an important source of polyclonal and monoclonal antibodies, adaptation of our FcRn overexpression technology in this species would bring significant advantages. We cloned the full length cDNA of the rabbit FcRn alpha-chain and found that it is similar to its orthologous analyzed so far. The rabbit FcRn - IgG contact residues are highly conserved, and based on this we predicted pH dependent interaction, which we confirmed by analyzing the pH dependent binding of FcRn to rabbit IgG using yolk sac lysates of rabbit fetuses by Western blot. Using immunohistochemistry, we detected strong FcRn staining in the endodermal cells of the rabbit yolk sac membrane, while the placental trophoblast cells and amnion showed no FcRn staining. Then, using BAC transgenesis we generated transgenic rabbits carrying and overexpressing a 110 kb rabbit genomic fragment encoding the FcRn. These transgenic rabbits – having one extra copy of the FcRn when hemizygous and two extra copies when homozygous - showed improved IgG protection and an augmented humoral immune response when immunized with a variety of different antigens. Our results in these transgenic rabbits demonstrate an increased immune response, similar to what we described in mice, indicating that FcRn overexpression brings significant advantages for the production of polyclonal and monoclonal antibodies.
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spelling pubmed-32561542012-01-13 Characterization of the Rabbit Neonatal Fc Receptor (FcRn) and Analyzing the Immunophenotype of the Transgenic Rabbits That Overexpresses FcRn Catunda Lemos, Ana Paula Cervenak, Judit Bender, Balázs Hoffmann, Orsolya Ivett Baranyi, Mária Kerekes, Andrea Farkas, Anita Bősze, Zsuzsanna Hiripi, László Kacskovics, Imre PLoS One Research Article The neonatal Fc receptor (FcRn) regulates IgG and albumin homeostasis, mediates maternal IgG transport, takes an active role in phagocytosis, and delivers antigen for presentation. We have previously shown that overexpression of FcRn in transgenic mice significantly improves the humoral immune response. Because rabbits are an important source of polyclonal and monoclonal antibodies, adaptation of our FcRn overexpression technology in this species would bring significant advantages. We cloned the full length cDNA of the rabbit FcRn alpha-chain and found that it is similar to its orthologous analyzed so far. The rabbit FcRn - IgG contact residues are highly conserved, and based on this we predicted pH dependent interaction, which we confirmed by analyzing the pH dependent binding of FcRn to rabbit IgG using yolk sac lysates of rabbit fetuses by Western blot. Using immunohistochemistry, we detected strong FcRn staining in the endodermal cells of the rabbit yolk sac membrane, while the placental trophoblast cells and amnion showed no FcRn staining. Then, using BAC transgenesis we generated transgenic rabbits carrying and overexpressing a 110 kb rabbit genomic fragment encoding the FcRn. These transgenic rabbits – having one extra copy of the FcRn when hemizygous and two extra copies when homozygous - showed improved IgG protection and an augmented humoral immune response when immunized with a variety of different antigens. Our results in these transgenic rabbits demonstrate an increased immune response, similar to what we described in mice, indicating that FcRn overexpression brings significant advantages for the production of polyclonal and monoclonal antibodies. Public Library of Science 2012-01-11 /pmc/articles/PMC3256154/ /pubmed/22247762 http://dx.doi.org/10.1371/journal.pone.0028869 Text en Catunda Lemos et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Catunda Lemos, Ana Paula
Cervenak, Judit
Bender, Balázs
Hoffmann, Orsolya Ivett
Baranyi, Mária
Kerekes, Andrea
Farkas, Anita
Bősze, Zsuzsanna
Hiripi, László
Kacskovics, Imre
Characterization of the Rabbit Neonatal Fc Receptor (FcRn) and Analyzing the Immunophenotype of the Transgenic Rabbits That Overexpresses FcRn
title Characterization of the Rabbit Neonatal Fc Receptor (FcRn) and Analyzing the Immunophenotype of the Transgenic Rabbits That Overexpresses FcRn
title_full Characterization of the Rabbit Neonatal Fc Receptor (FcRn) and Analyzing the Immunophenotype of the Transgenic Rabbits That Overexpresses FcRn
title_fullStr Characterization of the Rabbit Neonatal Fc Receptor (FcRn) and Analyzing the Immunophenotype of the Transgenic Rabbits That Overexpresses FcRn
title_full_unstemmed Characterization of the Rabbit Neonatal Fc Receptor (FcRn) and Analyzing the Immunophenotype of the Transgenic Rabbits That Overexpresses FcRn
title_short Characterization of the Rabbit Neonatal Fc Receptor (FcRn) and Analyzing the Immunophenotype of the Transgenic Rabbits That Overexpresses FcRn
title_sort characterization of the rabbit neonatal fc receptor (fcrn) and analyzing the immunophenotype of the transgenic rabbits that overexpresses fcrn
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256154/
https://www.ncbi.nlm.nih.gov/pubmed/22247762
http://dx.doi.org/10.1371/journal.pone.0028869
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