IgG, a monomer, is the predominant Ig class present in human serum. Produced as part of the secondary immune response to an antigen, this class of immunoglobulin constitutes approximately 75% of total serum Ig. IgG is the only class of Ig that can cross the placenta in humans, and it is largely responsible for protection of the newborn during the first months of life. Because of its relative abundance and excellent specificity toward antigens, IgG is the principal antibody used in immunological research and clinical diagnostics.
Properties of IgG:
- Molecular weight: 150,000 Da
- H-chain type (MW): gamma (53,000 Da)
- Serum concentration: 10 to 16 mg/mL
- Percent of total immunoglobulin: 75%
- Glycosylation (by weight): 3%
- Distribution: intra- and extravascular
- Function: secondary response
The role of IgG in the immune response
IgG is the major immunoglobulin in blood, lymph fluid, cerebrospinal fluid and peritoneal fluid and a key player in the humoral immune response. Serum IgG in healthy humans presents approximately 15% of total protein beside albumins, enzymes, other globulins, and many more.
The Fc portion of IgG, but not F(ab´)2 or Fab fragments, can cross the placenta of a mother and enter fetal circulation, providing the fetus with postpartum protection. IgG molecules are able to react with Fcγ receptors that are present on the surface of macrophages, neutrophils and natural killer cells, and can activate the complement system.
The binding of the Fc portion of IgG to the receptor present on a phagocyte is a critical step in the opsonization. Phagocytosis of particles coated with IgG antibodies is a vital mechanism that cells use to cope with microorganisms.
IgG is produced in a delayed response to an infection and can be retained in the body for a long time. The longevity in serum makes IgG most useful for passive immunization by transfer of this antibody. Detection of IgG usually indicates a prior infection or vaccination.
There are four IgG subclasses described in human, mouse and rat. The subclasses differ in the number of disulfide bonds and the length and flexibility of the hinge region. Except for their variable regions, all immunoglobulins within one class share about 90% homology, but only 60% among classes.
Determination of IgG subclasses can be a valuable tool in indicating a potential antibody deficiency. Selective IgG subclass deficiencies are associated with disease. In cases with prolonged or severe infections, determination of IgG levels can provide additional insight into the manifestation of disease. It is important to interpret IgG subclass concentrations in correlation to the donor's age since the immune system matures during childhood.
Because of its relative abundance and excellent specificity toward antigens, IgG is the principal antibody used in immunological research and clinical diagnostics.
IgG1 comprises 60–65% of the total main subclass IgG, and is predominantly responsible for the thymus-mediated immune response against proteins and polypeptide antigens. IgG1 binds to the Fc-receptor of phagocytic cells and can activate the complement cascade via binding to C1 complex. IgG1 immune response can already be measured in newborns and reaches its typical concentration in infancy. A deficiency in IgG1 isotype is typically a sign of a hypogammaglobulinemia.
IgG2, the second largest of IgG isotypes, comprises 20–25% of the main subclass and is the prevalent immune response against carbohydrate/polysaccharide antigens. “Adult” concentrations are usually reached by 6 or 7 years old. Among all IgG isotype deficiencies, a deficiency in IgG2 is the most common and is associated with recurring airway/respiratory infections in infants.
IgG3 comprises around 5–10% of total IgG and plays a major role in the immune responses against protein or polypeptide antigens. The affinity of IgG3 can be higher than that of IgG1.
Comprising usually less than 4% of total IgG, IgG4 does not bind to polysaccharides. In the past, testing for IgG4 has been associated with food allergies, and recent studies have shown that elevated serum levels of IgG4 are found in patients suffering from sclerosing pancreatitis, cholangitis and interstitial pneumonia caused by infiltrating IgG4 positive plasma cells. The precise role of IgG4 is still mostly unknown.