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

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.

• Authors: 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 Coward, Qingshun Lin, Sachiko Hirose, Daniela Salvatori, Thorbald van Hall, Cees van Kooten, Piero Mastroeni, Ferry Ossendorp, J Sjef Verbeek
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 200 Issue 8 Pg. 2615-2626 (04 15 2018) ISSN: 1550-6606 [Electronic] United States
• PMID: 29523656 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 by The American Association of Immunologists, Inc.