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A human immune system (HIS) mouse model that dissociates roles for mouse and human FcR + cells during antibody-mediated immune responses

European journal of immunology, 2023-12, Vol.53 (12), p.e2350454 [Peer Reviewed Journal]

2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. ;Attribution - NonCommercial - NoDerivatives ;ISSN: 0014-2980 ;EISSN: 1521-4141 ;DOI: 10.1002/eji.202350454 ;PMID: 37621208

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Title:
A human immune system (HIS) mouse model that dissociates roles for mouse and human FcR + cells during antibody-mediated immune responses
Author: Thaller, Anna Louisa ; Jönsson, Friederike ; Fiquet, Oriane ; Marie, Solenne ; Doisne, Jean-Marc ; Girelli-Zubani, Giulia ; Eri, Toshiki ; Fernandes, Priyanka ; Tatirovsky, Evgeny ; Langa-Vives, Francina ; Bruhns, Pierre ; Strick-Marchand, Hélène ; Di Santo, James P
Subjects: Adaptive Immunity ; Animals ; Antibody-Dependent Cell Cytotoxicity ; Complement System Proteins ; Humans ; Immunoglobulin G ; Life Sciences ; Macrophages ; Mice ; Receptors, Fc ; Receptors, IgG - genetics
Is Part Of: European journal of immunology, 2023-12, Vol.53 (12), p.e2350454
Description: 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.
Publisher: Germany: Wiley-VCH Verlag
Language: English
Identifier: ISSN: 0014-2980
EISSN: 1521-4141
DOI: 10.1002/eji.202350454
PMID: 37621208
Source: Hyper Article en Ligne (HAL) (Open Access)

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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. ;Attribution - NonCommercial - NoDerivatives ;ISSN: 0014-2980 ;EISSN: 1521-4141 ;DOI: 10.1002/eji.202350454 ;PMID: 37621208

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