A human immune system (HIS) mouse model that dissociates roles for mouse and human FcR+ cells during antibody-mediated immune responses
© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH..
Human immune system (HIS) mice provide a model to study human immune responses in vivo. Currently available HIS mouse models may harbor mouse Fc Receptor (FcR)-expressing cells that exert potent effector functions following administration of human Ig. Previous studies showed that the ablation of the murine FcR gamma chain (FcR-γ) results in loss of antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis in vivo. We created a new FcR-γ-deficient HIS mouse model to compare host (mouse) versus graft (human) effects underlying antibody-mediated immune responses in vivo. FcR-γ-deficient HIS recipients lack expression and function of mouse activating FcRs and can be stably and robustly reconstituted with human immune cells. By screening blood B-cell depletion by rituximab Ig variants, we found that human FcγRs-mediated IgG1 effects, whereas mouse activating FcγRs were dominant in IgG4 effects. Complement played a role as an IgG1 variant (IgG1 K322A) lacking complement binding activity was largely ineffective. Finally, we provide evidence that FcγRIIIA on human NK cells could mediate complement-independent B-cell depletion by IgG1 K322A. We anticipate that our FcR-γ-deficient HIS model will help clarify mechanisms of action of exogenous administered human antibodies in vivo.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
European journal of immunology - 53(2023), 12 vom: 19. Dez., Seite e2350454 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Thaller, Anna Louisa [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.12.2023 Date Revised 20.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/eji.202350454 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Thaller, Anna Louisa |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A human immune system (HIS) mouse model that dissociates roles for mouse and human FcR+ cells during antibody-mediated immune responses |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. | ||
| 520 | |a Human immune system (HIS) mice provide a model to study human immune responses in vivo. Currently available HIS mouse models may harbor mouse Fc Receptor (FcR)-expressing cells that exert potent effector functions following administration of human Ig. Previous studies showed that the ablation of the murine FcR gamma chain (FcR-γ) results in loss of antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis in vivo. We created a new FcR-γ-deficient HIS mouse model to compare host (mouse) versus graft (human) effects underlying antibody-mediated immune responses in vivo. FcR-γ-deficient HIS recipients lack expression and function of mouse activating FcRs and can be stably and robustly reconstituted with human immune cells. By screening blood B-cell depletion by rituximab Ig variants, we found that human FcγRs-mediated IgG1 effects, whereas mouse activating FcγRs were dominant in IgG4 effects. Complement played a role as an IgG1 variant (IgG1 K322A) lacking complement binding activity was largely ineffective. Finally, we provide evidence that FcγRIIIA on human NK cells could mediate complement-independent B-cell depletion by IgG1 K322A. We anticipate that our FcR-γ-deficient HIS model will help clarify mechanisms of action of exogenous administered human antibodies in vivo | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ADCC | |
| 650 | 4 | |a Antibody-mediated immune responses | |
| 650 | 4 | |a Fc receptors | |
| 650 | 4 | |a Human immune system (HIS) mice | |
| 650 | 4 | |a NK cells | |
| 650 | 7 | |a Receptors, Fc |2 NLM | |
| 650 | 7 | |a Receptors, IgG |2 NLM | |
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| 650 | 7 | |a Complement System Proteins |2 NLM | |
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| 700 | 1 | |a Jönsson, Friederike |e verfasserin |4 aut | |
| 700 | 1 | |a Fiquet, Oriane |e verfasserin |4 aut | |
| 700 | 1 | |a Marie, Solenne |e verfasserin |4 aut | |
| 700 | 1 | |a Doisne, Jean-Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Girelli-Zubani, Giulia |e verfasserin |4 aut | |
| 700 | 1 | |a Eri, Toshiki |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandes, Priyanka |e verfasserin |4 aut | |
| 700 | 1 | |a Tatirovsky, Evgeny |e verfasserin |4 aut | |
| 700 | 1 | |a Langa-Vives, Francina |e verfasserin |4 aut | |
| 700 | 1 | |a Bruhns, Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Strick-Marchand, Hélène |e verfasserin |4 aut | |
| 700 | 1 | |a Di Santo, James P |e verfasserin |4 aut | |
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