Immunoglobulin G (IgG) is the most abundant class of antibody in human serum and a major component of adaptive immunity. It is a protein produced by plasma cells derived from activated B cells. IgG recognizes specific foreign substances and connects their recognition with mechanisms that neutralize or eliminate them. Humans have four IgG subclasses—IgG1, IgG2, IgG3, and IgG4—with different structural and functional properties. IgG also provides protection early in life through transfer from mother to fetus. (ncbi.nlm.nih.gov)
Molecular structure
A typical IgG molecule is a Y-shaped monomer of approximately 150 kilodaltons. It contains two identical gamma heavy chains and two identical light chains, held together by disulfide bonds and noncovalent interactions. Each light chain is either kappa or lambda. Variable regions at the tips of the arms form two binding sites for an antigen, while the remaining regions provide structural support and determine the antibody’s interactions with other immune components. (ncbi.nlm.nih.gov)
The arms are called Fab regions, meaning “fragment antigen-binding.” Each recognizes an epitope, a particular molecular feature of an antigen. The stem, called the Fc region or “fragment crystallizable,” interacts with receptors and immune proteins. A flexible hinge allows the arms to adopt different orientations. This division separates antigen recognition from effector function: antibodies with similar antigen-binding regions can have different biological effects when their constant regions differ. (ncbi.nlm.nih.gov)
Production and immune memory
B cells initially generate antigen-recognition diversity through rearrangement of antibody gene segments. Following activation, some undergo class-switch recombination, replacing the heavy-chain constant region associated with IgM with one associated with IgG. Switching changes the antibody class without itself changing the rearranged variable-region sequence. Signals from helper T cells and cytokines help regulate this process. (ncbi.nlm.nih.gov)
Activated B cells can differentiate into antibody-secreting plasma cells or memory B cells. During an immune response, somatic hypermutation and selection can improve antigen binding, a process called affinity maturation. These processes are distinct from class switching. Persistent antibody secretion and the capacity of memory cells to respond upon re-exposure contribute to immunological memory. Consequently, the persistence of an IgG response does not mean that individual antibody molecules remain indefinitely in circulation. (ncbi.nlm.nih.gov)
Functions in host defense
IgG contributes to defense through several mechanisms:
- Neutralization: Binding can prevent viruses or microbial toxins from interacting with their targets. This depends on the antigen-binding regions rather than necessarily requiring Fc-mediated activity. (ncbi.nlm.nih.gov)
- Opsonization: IgG coating a microorganism promotes recognition by immune cells through Fc-gamma receptors. This opsonization facilitates phagocytosis and destruction of the coated material. (pubmed.ncbi.nlm.nih.gov)
- Complement activation: Appropriately arranged antigen-bound IgG can engage C1q and initiate the classical pathway of the complement system, supporting microbial clearance. Subclasses differ in their ability to activate this pathway. (frontiersin.org)
- Cell-mediated killing: Fc-receptor-bearing cells can recognize IgG-coated target cells and trigger antibody-dependent cellular cytotoxicity. (pubmed.ncbi.nlm.nih.gov)
These functions link antigen-specific recognition to cellular and soluble defense mechanisms. Their strength depends on subclass, antigen arrangement, and receptor interactions, rather than on IgG concentration alone. (pubmed.ncbi.nlm.nih.gov)
Human subclasses
The four human subclasses differ principally in their heavy-chain constant regions, including hinge structure. IgG1 is the most abundant and commonly responds to protein antigens. IgG2 is particularly associated with responses to bacterial polysaccharides. IgG3 has a long hinge and strong complement-activating capacity. IgG4 generally does not activate classical complement and can exchange paired heavy-chain–light-chain units with other IgG4 molecules, producing antibodies whose two arms recognize different antigens. These are characteristic tendencies, not exclusive assignments of particular antigens to individual subclasses. (frontiersin.org)
Persistence and maternal transfer
The neonatal Fc receptor (FcRn) helps maintain IgG in circulation. It binds IgG in acidic intracellular compartments and redirects it away from degradation, allowing release back into the extracellular environment. IgG1, IgG2, and IgG4 typically have circulating half-lives of about three weeks. IgG3 commonly has a shorter half-life, although inherited variants can alter its persistence. Despite its name, FcRn functions throughout life. (pmc.ncbi.nlm.nih.gov)
IgG is the only antibody class transferred across the human placenta in substantial amounts. FcRn-mediated transport supplies the fetus with maternal antibodies, providing temporary passive protection after birth. Transfer increases as pregnancy progresses and depends on gestational age, maternal antibody levels, subclass, and placental condition. Maternal IgG subsequently declines as the infant develops its own antibody responses. Some harmful maternal antibodies can also cross the placenta. (pmc.ncbi.nlm.nih.gov)
Laboratory and therapeutic significance
Laboratory tests distinguish total IgG concentration from IgG directed against a particular antigen. Total IgG measurement contributes to assessment of immunodeficiency and abnormal immunoglobulin production. One commonly reported reference interval is 7–16 g/L, but reference limits vary among laboratories. Increased immunoglobulin concentrations can occur with chronic inflammatory conditions and blood or bone-marrow disorders, including multiple myeloma. A quantitative result alone does not establish a diagnosis. (medlineplus.gov)
Human immune-globulin preparations are used as antibody-replacement therapy in primary humoral immunodeficiency. Products are available for intravenous or subcutaneous administration. Some intravenous preparations also have approved indications involving immune-mediated disorders, such as immune thrombocytopenia and chronic inflammatory demyelinating polyneuropathy. The indications depend on the specific preparation; “IgG” describes the antibody class, not a single interchangeable medicinal product. (fda.gov)