Fully Human Herpesvirus-Specific Neutralizing IgG Antibodies Generated by EBV Immortalization of Splenocytes-Derived from Immunized Humanized Mice
Antiviral neutralizing antibodies (nAbs) are commonly derived from B cells developed in immunized or infected animals and humans. Fully human antibodies are preferred for clinical use as they are potentially less immunogenic. However, the function of B cells varies depending on their homing pattern...
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2023-12-01
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author | Sebastian J. Theobald Elena Fiestas Andreas Schneider Benjamin Ostermann Simon Danisch Constantin von Kaisenberg Jan Rybniker Wolfgang Hammerschmidt Reinhard Zeidler Renata Stripecke |
author_facet | Sebastian J. Theobald Elena Fiestas Andreas Schneider Benjamin Ostermann Simon Danisch Constantin von Kaisenberg Jan Rybniker Wolfgang Hammerschmidt Reinhard Zeidler Renata Stripecke |
author_sort | Sebastian J. Theobald |
collection | DOAJ |
description | Antiviral neutralizing antibodies (nAbs) are commonly derived from B cells developed in immunized or infected animals and humans. Fully human antibodies are preferred for clinical use as they are potentially less immunogenic. However, the function of B cells varies depending on their homing pattern and an additional hurdle for antibody discovery in humans is the source of human tissues with an immunological microenvironment. Here, we show an efficient method to pharm human antibodies using immortalized B cells recovered from Nod.Rag.Gamma (NRG) mice reconstituting the human immune system (HIS). Humanized HIS mice were immunized either with autologous engineered dendritic cells expressing the human cytomegalovirus gB envelope protein (HCMV-gB) or with Epstein–Barr virus-like particles (EB-VLP). Human B cells recovered from spleen of HIS mice were efficiently immortalized with EBV in vitro. We show that these immortalized B cells secreted human IgGs with neutralization capacities against prototypic HCMV-gB and EBV-gp350. Taken together, we show that HIS mice can be successfully used for the generation and pharming fully human IgGs. This technology can be further explored to generate antibodies against emerging infections for diagnostic or therapeutic purposes. |
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institution | Directory Open Access Journal |
issn | 2073-4409 |
language | English |
last_indexed | 2024-03-08T15:10:56Z |
publishDate | 2023-12-01 |
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series | Cells |
spelling | doaj.art-fbf2eb71ec7849e58367a95268336eee2024-01-10T14:53:13ZengMDPI AGCells2073-44092023-12-011312010.3390/cells13010020Fully Human Herpesvirus-Specific Neutralizing IgG Antibodies Generated by EBV Immortalization of Splenocytes-Derived from Immunized Humanized MiceSebastian J. Theobald0Elena Fiestas1Andreas Schneider2Benjamin Ostermann3Simon Danisch4Constantin von Kaisenberg5Jan Rybniker6Wolfgang Hammerschmidt7Reinhard Zeidler8Renata Stripecke9Department I of Internal Medicine, University Hospital Cologne, Faculty of Medicine, University of Cologne, 50937 Cologne, GermanyResearch Unit Gene Vectors, Helmholtz Center Munich, German Research Center for Environmental Health, 81377 Munich, GermanyClinic of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, GermanyClinic of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, GermanyClinic of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, GermanyDepartment of Obstetrics, Gynecology and Reproductive Medicine, Hannover Medical School, 30625 Hannover, GermanyDepartment I of Internal Medicine, University Hospital Cologne, Faculty of Medicine, University of Cologne, 50937 Cologne, GermanyResearch Unit Gene Vectors, Helmholtz Center Munich, German Research Center for Environmental Health, 81377 Munich, GermanyGerman Center for Infection Research (DZIF), Partner Site Munich, 81377 Munich, GermanyDepartment I of Internal Medicine, University Hospital Cologne, Faculty of Medicine, University of Cologne, 50937 Cologne, GermanyAntiviral neutralizing antibodies (nAbs) are commonly derived from B cells developed in immunized or infected animals and humans. Fully human antibodies are preferred for clinical use as they are potentially less immunogenic. However, the function of B cells varies depending on their homing pattern and an additional hurdle for antibody discovery in humans is the source of human tissues with an immunological microenvironment. Here, we show an efficient method to pharm human antibodies using immortalized B cells recovered from Nod.Rag.Gamma (NRG) mice reconstituting the human immune system (HIS). Humanized HIS mice were immunized either with autologous engineered dendritic cells expressing the human cytomegalovirus gB envelope protein (HCMV-gB) or with Epstein–Barr virus-like particles (EB-VLP). Human B cells recovered from spleen of HIS mice were efficiently immortalized with EBV in vitro. We show that these immortalized B cells secreted human IgGs with neutralization capacities against prototypic HCMV-gB and EBV-gp350. Taken together, we show that HIS mice can be successfully used for the generation and pharming fully human IgGs. This technology can be further explored to generate antibodies against emerging infections for diagnostic or therapeutic purposes.https://www.mdpi.com/2073-4409/13/1/20HCMVEBVherpesvirushumanized miceantibodiesimmortalization |
spellingShingle | Sebastian J. Theobald Elena Fiestas Andreas Schneider Benjamin Ostermann Simon Danisch Constantin von Kaisenberg Jan Rybniker Wolfgang Hammerschmidt Reinhard Zeidler Renata Stripecke Fully Human Herpesvirus-Specific Neutralizing IgG Antibodies Generated by EBV Immortalization of Splenocytes-Derived from Immunized Humanized Mice Cells HCMV EBV herpesvirus humanized mice antibodies immortalization |
title | Fully Human Herpesvirus-Specific Neutralizing IgG Antibodies Generated by EBV Immortalization of Splenocytes-Derived from Immunized Humanized Mice |
title_full | Fully Human Herpesvirus-Specific Neutralizing IgG Antibodies Generated by EBV Immortalization of Splenocytes-Derived from Immunized Humanized Mice |
title_fullStr | Fully Human Herpesvirus-Specific Neutralizing IgG Antibodies Generated by EBV Immortalization of Splenocytes-Derived from Immunized Humanized Mice |
title_full_unstemmed | Fully Human Herpesvirus-Specific Neutralizing IgG Antibodies Generated by EBV Immortalization of Splenocytes-Derived from Immunized Humanized Mice |
title_short | Fully Human Herpesvirus-Specific Neutralizing IgG Antibodies Generated by EBV Immortalization of Splenocytes-Derived from Immunized Humanized Mice |
title_sort | fully human herpesvirus specific neutralizing igg antibodies generated by ebv immortalization of splenocytes derived from immunized humanized mice |
topic | HCMV EBV herpesvirus humanized mice antibodies immortalization |
url | https://www.mdpi.com/2073-4409/13/1/20 |
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