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A Restricted Role for FcgammaR in the Regulation of Adaptive Immunity
Leiden University Medical Center, ZA Leiden, the Netherlands.
Leiden University Medical Center, ZA Leiden, the Netherlands.
Leiden University Medical Center, ZA Leiden, the Netherlands.
Leiden University Medical Center, ZA Leiden, the Netherlands.
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2018 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 200, no 8, p. 2615-2626Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
2018. Vol. 200, no 8, p. 2615-2626
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Immunology in the medical area
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URN: urn:nbn:se:hh:diva-48897DOI: 10.4049/jimmunol.1700429PubMedID: 29523656OAI: oai:DiVA.org:hh-48897DiVA, id: diva2:1717823
Available from: 2022-12-09 Created: 2022-12-09 Last updated: 2023-03-07Bibliographically approved

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Nandakumar, Kutty Selva

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