Fc Receptors for Immunoglobulins and Their Appearance during Vertebrate Evolution

Abstract

Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR γ chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

Antibody Isotypes for Tumor Immunotherapy

“…These networks are partially conserved between different species, even though also many critical differences have evolved [10]. These species specific characteristics need to be considered in the interpretation of results from in vivo experiments [11,12].…”

Biophysical and Biochemical Characterization of Avian Secretory Component Provides Structural Insights into the Evolution of the Polymeric Ig Receptor

“…Together, these molecules protect vertebrates from the external environment, excluding pathogenic and toxic agents while also promoting host-bacterial mutualism with commensal agents (3). The pIgR is the earliest recognizable antibody Fc receptor, and along with its polymeric Immunoglobulin (pIg) ligands, is conserved from teleost (bony) fish to mammals (5). The pIgR has an extracellular region composed of tandem immunoglobulin-like (Ig-like) domains, a transmembrane region and a cytoplasmic tail (6); however, the domain organization of the extracellular region (hereafter referred to as secretory component; SC) is divergent among species (5,7) (Fig.…”

“…In amphibians, the pIgR ectodomain contains four Ig-like domains (D1-D4) that bind polymeric forms of IgM and IgX, an amphibian mucosal antibody (10). Similar to amphibians, avian and reptilian pIgR also contain four extracellular domains, but bind to polymeric forms of IgM and IgA (pIgA), which assemble together with a protein called joining (J) chain (5,7,11). Mammalian SC also bind pIgs, typically dimeric IgA (dIgA) and pentameric IgM (pIgM), however a gene duplication event added a domain immediately following D1, enlarging mammalian SC to five Ig-like domains (D1-D5) (5,6).…”

“…Similar to amphibians, avian and reptilian pIgR also contain four extracellular domains, but bind to polymeric forms of IgM and IgA (pIgA), which assemble together with a protein called joining (J) chain (5,7,11). Mammalian SC also bind pIgs, typically dimeric IgA (dIgA) and pentameric IgM (pIgM), however a gene duplication event added a domain immediately following D1, enlarging mammalian SC to five Ig-like domains (D1-D5) (5,6). Phylogenic sequence analysis suggests that fish D1-D2 are homologous to mammalian D1 and D5, while avian D1-D2-D3-D4 are homologous to mammalian D1-D3-D4-D5 (8,12–14).…”

Short-Term Regulation of FcγR-Mediated Phagocytosis by TLRs in Macrophages: Participation of 5-Lipoxygenase Products

“…Ingestion via the Fc γ R is important not only for antibody-mediated phagocytosis of microbes but also for antigen processing and presentation to T cells [2]. Thereby, Fc γ Rs contribute to expanding, sustaining, and regulating immune responses [3].…”