期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 -, 期 -, 页码 -出版社
WILEY
DOI: 10.1002/eji.202350454
关键词
ADCC; NK cells; Antibody-mediated immune responses; Fc receptors; Human immune system (HIS) mice
类别
Human immune system (HIS) mice are used to study human immune responses in vivo. A new FcR-γ-deficient HIS mouse model was created to compare host (mouse) versus graft (human) effects in antibody-mediated immune responses in vivo.
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-?) results in loss of antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis in vivo. We created a new FcR-?-deficient HIS mouse model to compare host (mouse) versus graft (human) effects underlying antibody-mediated immune responses in vivo. FcR-?-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 Fc?Rs-mediated IgG1 effects, whereas mouse activating Fc?Rs 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 Fc?RIIIA on human NK cells could mediate complement-independent B-cell depletion by IgG1 K322A. We anticipate that our FcR-?-deficient HIS model will help clarify mechanisms of action of exogenous administered human antibodies in vivo.
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