Five major classes of Antibodies and their Biological Activities

Heavy-chain sequence analysis of an immunoglobulin molecule revealed five basic sequence patterns.
These five basic sequences correspond to five different heavy-chain constant (C) regions named with Greek letters: μ (mu), 𝛿 (delta), γ (gamma), ε (epsilon), and α (alpha).
Each of these five different heavy chains is called an isotype which determines the class of the given antibody molecule.
There are five major classes of antibodies: IgM, IgG, IgA, IgD and IgE.
Minor differences in the amino acid sequences of the heavy chains (α and γ), leads to further classification of the heavy chains into sub-isotypes.
Sub-isotypes determine the subclass of the antibody molecules they constitute.
The molecular properties and biological activities of the immunoglobulin classes are summarized below:

1. Immunoglobulin G (IgG):

IgG consists of two Gamma(γ) heavy-chains (50 KDa each) and two Kappa (k) or two Lambda (λ) light-chains (25 KDa each).
Total molecular weight: 150 KDa
It is the most abundant class of Immunoglobulin in serum constituting of about 80% of total serum immunoglobulin.
There are four human IgG subclasses based on the differences in Y-chain (Y1, Y2, y3 and Y4) constant region sequences which are numbered according to their decreasing average serum concentrations: IgG1, IgG2, IgG3 and IgG4,
Each of IgG subclasses has a molecular weight of about 150 KDa.
It has the longest half-life (23 days) among all antibodies.

Biological activities:

IgG1, IgG3 and IgG4 readily cross the placenta and provide immunity to the developing fetus up to 6 months.
IgG also activates complement proteins. IgG3 is the most effective complement activator followed by IgG1 and IgG2. IgG4 cannot activate complement proteins.
IgG1 and IgG3 mediate opsonization by binding with Fc receptors on phagocytic cells.
IgG helps in bacterial immobilization.
It also neutralizes toxin and viruses.
It is the major antibody produced during secondary immune response.

2. Immunoglobulin M (IgM):

It exists as a pentamer (900 KDa) in which five monomeric units (180 KDa each) are held together by disulfide bonds.
It consists of 10 Mu (µ) heavy-chains (65 KDa each) and 10 k or 10 λ light-chains (25 KDa each).
There are 10 antigen binding sites (Fab) in a pentameric IgM molecule but due to steric hindrance it cannot bind to all 10 complete antigens at the same time.
The average serum concentration of IgM is about 1.5mg/dl that accounts for about 5-10% of total serum Immunoglobulin.
Each pentamer contains an additional Fc-linked polypeptide chain called the J-chain which is required for the polymerization of IgM.
It is secreted by plasma cells and expressed as membrane-bound antibody on B-cells.

Biological activities:

IgM is the first antibody produced during a primary immune response.
It is also the first antibody class produced by neonates.
Since IgM is in a pentameric form, it has higher number of antigen binding sites.
IgM is very effective in agglutination reaction. It takes 100 to 1000 times more molecules of IgG than of IgM to achieve the same level of agglutination.
IgM is more efficient than IgG in complement activation.
The presence of J-chain allows IgM to bind to the receptors on secretory cells and cross the epithelial linings to enter the external secretions.

3. Immunoglobulin A (IgA):

It primarily exists as a monomer in blood and consists of two Alpha (α) heavy chains (55 KDa each) and two k or two λ light chains (25 KDa each).
Dimeric, trimeric and some tetrameric forms of IgA are present in body secretions.
Its molecular weight ranges from 150 KDa to 600 KDa depending on its form.
IgA constitutes about 10-15% of total serum immunoglobulin.
Dimeric form of IgA contains J-chain and a secretory chain. Secretory chain helps IgA cross the epithelial layer and enter into body secretions, a process called transcytosis.
Capable of transcytosis, IgA is present in external secretions like breast milk, saliva, tears and mucus of bronchial, genitourinary and digestive tracts.
There are two sub-classes of IgA based on sub-isotypes of α heavy chain. i.e. IgA1 and IgA2.

Biological activities:

IgA provides local immunity in GI tracts, respiratory tract, genital tract etc. since it can cross the epithelial layer and enter into body secretion.
Binding of secretory IgA to bacterial and viral surface antigens prevents further attachment of the pathogens to the mucosal cells, thus inhibiting viral infection and bacterial colonization.

4. Immunoglobulin E (IgE):

It consists of two Epsilon (ε) heavy-chains (70 KDa each) and two k or two λ light chains (25 KDa each).
Total molecular weight: 190 KDa.
IgE constitutes about 0.3% of total serum Immunoglobulin.
Level of IgE in blood of normal individual is very low and its level increases during parasitic infection and in allergic reactions.
Because of its involvement in allergic reactions, it is also called a reagenic antibody.
Fc region of IgE present in Ag-Ab complex binds on blood basophils and tissue mast cells. This cross reaction causes degranulation of mast cell and basophils releasing histamine. Histamine is responsible for symptoms of allergy.

Biological activities:

IgE mediates immediate hypersensitivity reaction and responsible for symptoms like hay fever, asthma, anaphylactic shocks, etc.
IgE provides immunity against parasites by antibody dependent cell mediated cytotoxicity (ADCC).

5. Immunogloublin D (IgD):

It contains two Delta (𝛿) heavy chains (65 KDa each) and two k or two λ light chains (25 KDa each).
Molecular weight is 180 KDa.
It constitutes about 0.2% of total serum immunoglobulin.

Biological activities:

IgD, together with IgM, is the major membrane-bound immunoglobulin expressed by mature B-cells.
IgD plays an important role in maturation and proliferation of B-cell.
No other biological effector function has been identified for IgD.

Five major classes of Antibodies and their Biological Activities:

References:

https://www.ncbi.nlm.nih.gov/books/NBK27144/Immunobiology: The Immune System in Health and Disease. 5th edition
Kindt T. J, Goldsby R. A & Osbotne B. A, (sixth edition). Kuby Immunology, New York , NY: W.H. Freeman and Company, 2007

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