A Restricted Role for FcγR in the Regulation of Adaptive Immunity.
Authors
Fransen, Marieke F
van Maren, Wendy W
Sow, Heng Sheng
Breukel, Cor
Claassens, Jill WC
Brouwers, Conny
van der Kaa, Jos
Camps, Marcel
Vonk, Kelly K
van Heiningen, Sandra
Klar, Ngaisah
van Beek, Lianne
van Harmelen, Vanessa
Daxinger, Lucia
Coward, Chris
Lin, Qingshun
Hirose, Sachiko
Salvatori, Daniela
Ossendorp, Ferry
Publication Date
2018-04-15Journal Title
J Immunol
ISSN
0022-1767
Publisher
The American Association of Immunologists
Volume
200
Issue
8
Pages
2615-2626
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Fransen, M. F., Benonisson, H., van Maren, W. W., Sow, H. S., Breukel, C., Linssen, M. M., Claassens, J. W., et al. (2018). A Restricted Role for FcγR in the Regulation of Adaptive Immunity.. J Immunol, 200 (8), 2615-2626. https://doi.org/10.4049/jimmunol.1700429
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.
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/I002189/1)
Identifiers
External DOI: https://doi.org/10.4049/jimmunol.1700429
This record's URL: https://www.repository.cam.ac.uk/handle/1810/282851
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