Immunoglobulin G

IgG is a monomeric antibody composed of two heavy chains (γ) and two light chains (κ or λ), arranged in a Y shape. The variable regions at the tips of the Y bind specific antigens, while the constant Fc region mediates effector functions. IgG activates the classical complement pathway via C1q binding, leading to opsonization and lysis of pathogens. It also binds to Fc gamma receptors on macrophages and natural killer cells, triggering phagocytosis and antibody-dependent cellular cytotoxicity (ADCC).

The four subclasses—IgG1, IgG2, IgG3, and IgG4—differ in their heavy chain constant regions, hinge flexibility, and effector functions. IgG1 and IgG3 are potent complement activators, whereas IgG2 primarily targets bacterial capsular polysaccharides, and IgG4 is associated with allergic responses and immune tolerance. These differences are clinically relevant in vaccine responses and autoimmune diseases.

IgG deficiency leads to primary immunodeficiency syndromes, such as common variable immunodeficiency (CVID), characterized by recurrent bacterial infections. Measurement of IgG subclasses helps diagnose specific antibody deficiencies, and intravenous immunoglobulin (IVIG) therapy is used to replace missing antibodies in these patients.

Elevated IgG levels occur in chronic infections, autoimmune diseases like systemic lupus erythematosus, and multiple myeloma. IgG antibodies are also the basis of serological tests for past infection or vaccination, and they are the primary target of therapeutic monoclonal antibodies, including those used in cancer immunotherapy. In pregnancy, maternal IgG crosses the placenta via FcRn receptors, protecting the newborn until its own immune system matures.

IgG is the hallmark of the secondary immune response, produced in large quantities after memory B cells are reactivated. Vaccines aim to generate high-affinity IgG that neutralizes pathogens and provides long-lasting immunity. For example, the measles-mumps-rubella (MMR) vaccine induces protective IgG titers that persist for decades.

IgG also plays a role in mucosal immunity, though IgA is more prominent. In the gut, IgG can neutralize toxins and viruses, and in the respiratory tract, it contributes to protection against influenza and SARS-CoV-2. The development of IgG avidity assays helps distinguish recent from past infections, which is useful in diagnosing congenital infections like toxoplasmosis.

IgG has a unique recycling mechanism via the neonatal Fc receptor (FcRn), which rescues IgG from lysosomal degradation, giving it a long half-life of about 21 days in humans. This property is exploited in the design of therapeutic antibodies with extended half-lives.

IgG4 undergoes Fab-arm exchange, a process where half-molecules swap between different IgG4 antibodies, making them bispecific and functionally monovalent. This phenomenon is relevant in allergy and in the mechanism of action of some immunotherapies. Additionally, IgG can be transferred from mother to infant through breast milk, though at lower levels than IgA, providing passive protection in the neonatal gut. Rare IgG allotypes, such as Gm markers, are used in forensic science and population genetics to trace human migration patterns.

Opsonization

The process by which antibodies coat pathogens to enhance phagocytosis.

Complement system

A cascade of proteins that aids in pathogen destruction and inflammation.

FcRn

Neonatal Fc receptor that protects IgG from degradation and mediates transcytosis.

Fab-arm exchange

A unique IgG4 phenomenon where half-molecules swap, producing bispecific antibodies.