A restricted role for FcgR in the regulation of adaptive immunity

Marieke F. Fransen, Hreinn Benonisson, Wendy W. van Maren, Heng Sheng Sow, Cor Breukel, Margot M. Linssen, Jill W. C. Claassens, Conny Brouwers, Jos van der Kaa, Marcel Camps, Jan Willem Kleinovink, Kelly K. Vonk, Sandra van Heiningen, Ngaisah Klar, Lianne van Beek, Vanessa van Harmelen, Lucia Daxinger, Kutty S. Nandakumar, Rikard Holmdahl, Chris CowardQingshun Lin, Sachiko Hirose, Daniela Salvatori, Thorbald van Hall, Cees van Kooten, Piero Mastroeni, Ferry Ossendorp, J. Sjef Verbeek

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

By their interaction with IgG immune complexes, FcgR 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 FcgR-knockout mice, it has been concluded that FcgRs 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 FcgRs (FcgRI/II/III/IV 2 / 2 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 FcgRIIb-deficient mice, FcgRI/II/III/IV 2 / 2 mice developed higher Ab titers but no autoantibodies. These observations indicate a redundant role for activating FcgRs in the modulation of the adaptive immune response in vivo. We conclude that FcgRs 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.
Original languageEnglish
Pages (from-to)2615-2626
JournalJournal of Immunology
Volume200
Issue number8
DOIs
Publication statusPublished - 2018
Externally publishedYes

Cite this

Fransen, M. F., Benonisson, H., van Maren, W. W., Sow, H. S., Breukel, C., Linssen, M. M., ... Verbeek, J. S. (2018). A restricted role for FcgR in the regulation of adaptive immunity. Journal of Immunology, 200(8), 2615-2626. https://doi.org/10.4049/jimmunol.1700429