IgG
IgG, the key factor of Humoral immunity response, is the main immunoglobulin in blood, lymph, cerebrospinal fluid and peritoneal fluid. IgG accounts for approximately 75% of total serum immunoglobulins and is the only immunoglobulin that can penetrate the human placenta. It is primarily responsible for protecting newborns in the first few months of life. IgG can be further divided into four subtypes. It was discovered after extensive research on human IgG myeloma protein with specific rabbit Antiserum in the 1960s. It is named IgG1, IgG2, IgG3 and IgG4 according to the descending order of abundance [1]. The IgG subtype is composed of four subunits, including two heavy chains and two light chains. Each subunit is composed of a variable region and a constant region. A variable region determines their specificity for binding to antigens, while the constant region determines their biological function. In addition, the four IgG subtypes differ in terms of the number of disulfide bonds, the length and flexibility of the hinge region. Except for the variable region, all immunoglobulins in a subtype have approximately 90% homology, and approximately 60% homology between subtypes.
IgG antibodies mainly protect the body from infection by combining with anti-original neutralizing pathogens, activating the Complement system, mediating cytotoxicity and regulating immune response. In cases of long-term or severe infection, the determination of IgG levels can further understand the manifestations of the disease.
The properties of IgG are shown in Table 1. Due to the relative abundance and high specificity of antigens, IgG has become the main antibody used in immunological research and clinical diagnosis.
Table 1: Properties of IgG
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TIgG1
Immunoglobulin G1(IgG1), accounts for 60-65% of the total serum IgG levels [2]. IgG1 plays a crucial role in human immune response, which can cross the placenta and enter the fetal circulatory system to provide Passive immunity protection [2].
In addition to immune function, IgG1 is also involved in other biological processes, such as inflammatory reactions, autoimmune diseases, and allergic reactions. In certain diseases, the abnormal level of IgG1 can be used as an indicator for diagnosing and monitoring disease progression.
IgG2
Immunoglobulin G2(IgG2), accounts for 20-25% of the total serum IgG levels [2]. IgG2 also has strong anti-polysaccharide antigen ability [3-4] and plays an important role in some bacterial and fungal infections. Compared with other IgG subtypes, IgG2 is weaker in activating the Complement system and mediating cytotoxicity, but stronger in neutralizing polysaccharide antigens. This makes IgG2 play an important role in combating the infection of polysaccharide antigens and preventing diseases such as pneumococcal and influenza viruses.
Among all IgG homotypic deficiencies, IgG2 deficiency is the most common. It is associated with recurrent respiratory infections in infants.
IgG3
Immunoglobulin G3(IgG3), accounts for 5-10% of the total serum IgG levels [2]. Compared with other IgG subtypes, IgG3 has stronger antigen binding ability, which enables it to neutralize pathogens and toxins more effectively. In addition, IgG3 can activate the Complement system, promote cytotoxicity, and participate in the regulation of inflammatory response.
IgG3 also has some special characteristics. Firstly, its half-life is relatively short, approximately 21 days, which is shorter than other IgG subtypes. Secondly, IgG3 is relatively large in structure and has a longer inter subunit linkage region, which may affect its distribution and function within the organization.
IgG3 is particularly effective in Inductive effect function. As an effective pro-inflammatory antibody, its short half-life may limit the possibility of excessive inflammatory response [5].
IgG4
Immunoglobulin G4(IgG4), accounts for 3-6% of the total serum IgG levels [2]. IgG4 plays a special role in the immune response. Compared with other IgG subtypes, its antigen binding ability is weak, and it is less involved in neutralizing pathogens. On the contrary, IgG4 mainly exerts its effects by inhibiting immune responses. It can form double stranded antibodies with other IgG subtypes, and this antibody structure is called "Fab arm exchange" or "2:2 exchange". This exchange enables IgG4 to neutralize immune responses and regulate inflammatory responses, thereby reducing tissue damage. IgG4 also has the function of immune regulation. It can inhibit the function of other IgG subtypes and inhibit the activity of inflammatory cells. This regulatory effect may play an important role in the development of certain inflammatory diseases.
References
1. Schur PH. IgG subclasses. A historical perspective. Monogr Allergy (1988) 23:1–11.
2. Jefferis R, Kumararatne DS. Selective IgG subclass deficiency: quantification and clinical relevance. Clin Exp Immunol (1990) 81(3):357–67. doi:10.1111/j.1365-2249.1990.tb05339.x
3. Barrett DJ, Ayoub EM. IgG2 subclass restriction of antibody to pneumococcal polysaccharides. Clin Exp Immunol (1986) 63(1):127–34.
4. Kuijpers TW, Weening RS, Out TA. IgG subclass deficiencies and recurrent pyogenic infections, unresponsiveness against bacterial polysaccharide antigens. Allergol Immunopathol (Madr) (1992) 20(1):28–34.
Vidarsson G, Dekkers G and Rispens T (2014) IgG subclasses and allotypes: from structure to effector functions. Front. Immunol. 5:520. doi: 10.3389/fimmu.2014.00520