A Restricted Role for Fc gamma R in the Regulation of Adaptive Immunity

作者：Fransen, Marieke F.; Benonisson, Hreinn; van Maren, Wendy W.; Sow, Heng Sheng; Breuke, 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

来源：The Journal of Immunology, 2018, 200(8): 2615-2626.

DOI：10.4049/jimmunol.1700429

• DENDRITIC CELLS
• ANTIGEN PRESENTATION
• CROSS-PRESENTATION
• B-LYMPHOCYTES
• T-CELLS
• IN-VIVO
• COMPLEMENT
• ANTIBODIES
• MICE
• IGG

By their interaction with IgG immune complexes, Fc gamma R 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 Fc gamma R-knockout mice, it has been concluded that Fc gamma Rs 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 Fc gamma Rs (Fc gamma RI/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 Fc gamma RIIb-deficient mice, Fc gamma RI/II/III/IV-/- mice developed higher Ab titers but no autoantibodies. These observations indicate a redundant role for activating Fc gamma Rs in the modulation of the adaptive immune response in vivo. We conclude that Fc gamma Rs 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.

• 出版日期2018-4-15
• 单位南方医科大学