A Restricted Role for FcγR in the Regulation of Adaptive Immunity

• Published in: The Journal of immunology (1950) Vol. 200; no. 8; pp. 2615 - 2626
• Main Authors: Fransen, Marieke F, Benonisson, Hreinn, van Maren, Wendy W, Sow, Heng Sheng, Breukel, Cor, Linssen, Margot M, Claassens, Jill W C, Brouwers, Conny, van der Kaa, Jos, Camps, Marcel, Kleinovink, Jan Willem, Vonk, Kelly K, van Heiningen, Sandra, Klar, Ngaisah, van Beek, Lianne, van Harmelen, Vanessa, Daxinger, Lucia, Nandakumar, Kutty S, Holmdahl, Rikard, Coward, Chris, Lin, Qingshun, Hirose, Sachiko, Salvatori, Daniela, van Hall, Thorbald, van Kooten, Cees, Mastroeni, Piero, Ossendorp, Ferry, Verbeek, J Sjef
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 15-04-2018
• Subjects: Adaptive immunity; Antigen-antibody complexes; Autoantibodies; Experimental design; Immune response; Immunoglobulin G; Immunomodulation; Interferon; Medicin och hälsovetenskap; Mice; Ontogeny; Rodents; T cell receptors
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1700429

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.