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The complex role of Fcγ receptors in the pathology of arthritis

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Abstract

Autoantibodies of the IgG class and the immune complexes they form are central players in the pathology of rheumatoid arthritis (RA). Receptors for the Fc part of IgG, FcγR constitute one of the main effector mechanisms through which IgG immune complexes exert their action. The different members of the FcγR family exhibit extensive structural homology leading to redundancy in ligand specificity and signal transduction. Moreover, the initiation of effector mechanisms by IgG immune complexes can also be mediated by the complement system. This strong redundancy and high degree of complexity hampers a direct in vivo analysis of antibody effector pathways. Over the last decade, mice deficient for different combinations of FcγR have been generated by gene targeting. These knockout mice provide excellent tools to define the specific contribution of the different FcγR to IgG effector pathways in well-established in vivo mouse models for arthritis. This review will discuss the results of the studies that analyze the role of the different members of the FcγR family in murine arthritis models and their implications for our understanding of the human disease.

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Abbreviations

KO:

knockout

RANKL:

receptor activator of NFκB ligand

IL-1β:

interleukin-1β

Mϕ:

macrophage

DC:

dendritic cell

FDC:

follicular dendritic cell

bCII:

bovine type II collagen

ADCC:

antibody-dependent cell-mediated cytotoxicity

Th:

T helper cell

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Aknowledgements

We thank Drs. Alies Snijders, Andreea Ioan-Facsinay, and Victoria Arandhara for critical reading of the manuscript.

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  1. Department of Human Genetics, Leiden University Medical Center, Postzone S4-P P.O. Box 9600, 2300 RC, Leiden, The Netherlands

    Peter Boross & J. Sjef Verbeek

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Correspondence to J. Sjef Verbeek.

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Boross, P., Verbeek, J.S. The complex role of Fcγ receptors in the pathology of arthritis. Springer Semin Immun 28, 339–350 (2006). https://doi.org/10.1007/s00281-006-0049-9

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