Fc receptors as adaptive immunoreceptors - PubMed (original) (raw)

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Fc receptors as adaptive immunoreceptors

Marc Daëron. Curr Top Microbiol Immunol. 2014.

Abstract

Most biological activities of antibodies depend on their ability to engage Receptors for the Fc portion of immunoglobulins (FcRs) on a variety of cell types. As FcRs can trigger positive and negative signals, as these signals control several biological activities in individual cells, as FcRs are expressed by many cells of hematopoietic origin, mostly of the myeloid lineage, as these cells express various combinations of FcRs, and as FcR-expressing cells have different functional repertoires, antibodies can exert a wide spectrum of biological activities. Like B and T Cell Receptors (BCRs and TCRs), FcRs are bona fide immunoreceptors. Unlike BCRs and TCRs, however, FcRs are immunoreceptors with an adaptive specificity for antigen, with an adaptive affinity for antibodies, with an adaptive structure and with an adaptive signaling. They induce adaptive biological responses that depend on their tissue distribution and on FcR-expressing cells that are selected locally by antibodies. They critically determine health and disease. They are thus exquisitely adaptive therapeutic tools.

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Figures

Fig. 1

Fig. 1

Differential binding of antibodies and antigen to high-affinity and to low-affinity FcRs. Antibodies bind first to high-affinity FcRs, then antigen binds to receptor-bound antibodies (left). Antigen binds first to antibodies and form immune complexes that can then bind to low-affinity FcRs (right). The order of events is different but the result is the same: FcRs are aggregated

Fig. 2

Fig. 2

Modulation of the binding avidity with which immune complexes bind to FcRs. The binding avidity varies with the density of epitopes on antigen and with the density of FcRs on cell membranes

Fig. 3

Fig. 3

Trans- and cis-interactions of antibodies to cell surface antigens with FcR-expressing cells. Antibodies against antigens expressed by cell membranes can engage FcRs expressed by neighboring cells (trans-binding) or FcRs expressed on the membrane of the same cell (cis-binding)

Fig. 4

Fig. 4

Adaptive FcR complexes formed on cell surfaces upon receptor engagement. FcR complexes with variable compositions and sizes build up on cell membranes, depending on the FcRs expressed on cells, the isotypic composition of the antibody response, the local concentration of antibodies of the various classes and subclasses, the antigen specificity of these antibodies and the local concentration of antigen

Fig. 5

Fig. 5

Tissue distribution of FcRs and their engagement by antibodies of different classes. FcRs expressed by the various cell types in mice and humans are differentially engaged by antibodies of different classes. As a consequence, different cell types are involved

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