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Human antibodies are classified into five isotypes (IgM, IgD, IgG, IgA, and IgE) according to their H chains, which provide each isotype with distinct characteristics and roles.
IgG is the most abundant antibody isotype in the blood (plasma), accounting for 70-75% of human immunoglobulins (antibodies). IgG detoxifies harmful substances and is important in the recognition of antigen-antibody complexes by leukocytes and macrophages. IgG is transferred to the fetus through the placenta and protects the infant until its own immune system is functional.
IgM usually circulates in the blood, accounting for about 10% of human immunoglobulins. IgM has a pentameric structure in which five basic Y-shaped molecules are linked together. B cells produce IgM first in response to microbial infection/antigen invasion.
Although IgM has a lower affinity for antigens than IgG, it has higher avidity for antigens because of its pentameric/hexameric structure. IgM, by binding to the cell surface receptor, also activates cell signaling pathways.
IgA is abundant in serum, nasal mucus, saliva, breast milk, and intestinal fluid, accounting for 10-15% of human immunoglobulins. IgA forms dimers (i.e., two IgA monomers joined together). IgA in breast milk protects the gastrointestinal tract of neonates from pathogens.
IgE is present in minute amounts, accounting for no more than 0.001% of human immunoglobulins. Its original role is to protect against parasites. In regions where parasitic infection is rare, IgE is primarily involved in allergy.
IgD accounts for less than 1% of human immunoglobulins. IgD may be involved in the induction of antibody production in B cells, but its exact function remains unknown.
Immunoglobulin class switching
B cells expressing plasma membrane-bound IgM and IgD (mature B cells) are activated upon encounter with a specific antigen, and begin to proliferate and produce secretory IgM and IgD. With further activation by the antigen or other stimuli, these mature B cells differentiate into cells that produce increasing amounts of secreted immunoglobulins, and start to produce immunoglobulin isotypes other than IgM and IgD. This process is called “immunoglobulin class switching”.
Factors in the B cell environment (including hormones secreted by T cells [cytokines]) direct the isotype switching.
Interleukin 4 (IL4) stimulates class switching from IgM/IgD to IgG1 and IgE
Interleukin 5 (IL5) stimulates class switching from IgM/IgD to IgA
*Interleukins are a type of cytokine that is produced by leukocytes and lymphocytes during the immune response.