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

Fransen, Marieke F 
van Maren, Wendy W 
Sow, Heng Sheng 
Breukel, Cor 

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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.

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1107 Immunology, Biomedical, Basic Science, Inflammatory and Immune System, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors
Journal Title
J Immunol
Journal ISSN
Volume Title
The American Association of Immunologists
Biotechnology and Biological Sciences Research Council (BB/I002189/1)