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J Immunol. 2018 Apr 15;200(8):2615-2626. doi: 10.4049/jimmunol.1700429. Epub 2018 Mar 9.

A Restricted Role for FcγR in the Regulation of Adaptive Immunity.

Author information

1
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
2
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
3
Department of Nephrology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
4
Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.
5
School of Pharmaceutical Sciences, Southern Medical University, 510515 Guangzhou, China.
6
Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
7
Department of Pathology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
8
Toin Human Science and Technology Center, Department of Biomedical Engineering, Toin University of Yokohama, Yokohama 225-8502, Japan.
9
Department of Anatomy, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; and.
10
Department of Clinical Oncology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
11
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; j.s.verbeek@lumc.nl.

Abstract

By their interaction with IgG immune complexes, FcγR and complement link innate and adaptive immunity, showing functional redundancy. In complement-deficient mice, IgG downstream effector functions are often impaired, as well as adaptive immunity. Based on a variety of model systems using FcγR-knockout mice, it has been concluded that FcγRs are also key regulators of innate and adaptive immunity; however, several of the model systems underpinning these conclusions suffer from flawed experimental design. To address this issue, we generated a novel mouse model deficient for all FcγRs (FcγRI/II/III/IV-/- mice). These mice displayed normal development and lymphoid and myeloid ontogeny. Although IgG effector pathways were impaired, adaptive immune responses to a variety of challenges, including bacterial infection and IgG immune complexes, were not. Like FcγRIIb-deficient mice, FcγRI/II/III/IV-/- mice developed higher Ab titers but no autoantibodies. These observations indicate a redundant role for activating FcγRs in the modulation of the adaptive immune response in vivo. We conclude that FcγRs are downstream IgG effector molecules with a restricted role in the ontogeny and maintenance of the immune system, as well as the regulation of adaptive immunity.

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