- This type of immunoglobulin accounts or constitutes 5-10% of total serum immunoglobulin in adults.
- The serum concentration is 5-2 mg per 100 ml.
- The half-life of IgM is about 5 days.
- It can be produced in a T-independent manner.
- Monomeric IgM has molecular weight of 180,000 Da which is expressed as membrane bound antibody on B cells.
- It is often called macroglobulin and the millionaire molecule due to its high molecular weight.
- IgM is secreted by plasma cells as a pentamer in which five monomeric units are held together by disulfide bonds.
Image source: microbiologybook
- This bonds link their carboxyl-terminal heavy chains domains (Cµ4/Cµ4) and their Cµ3/Cµ3 domains.
- Fc regions of all the five monomeric subunits are arranged at the centre of the pentamer and also 10 antigen binding sites on the periphery of the molecule.
- An additional Fc-linked polypeptide called the J (joining) chain is also contained in each pentamer.
- This chain is disulfide-bonded to the carboxyl-terminal cysteine residue of two of the 10µ chains.
- For the polymerization of the monomers in order to form pentameric IgM, there is necessity of J chain, which is added just before the secretion of the pentamer.
- In a primary response to an antigen, IgM becomes the first immunoglobulin class to be produced.
- This is also the first immunoglobulin to be synthesized by neonate.
- IgM has the higher valency than the other isotypes due to its pentameric structure with 10 antigen-binding sites.
- 10 small hapten molecules can be bound by an IgM molecule but due to steric hindrance only five or fewer molecules of large antigens can be bound simultaneously.
- Pentameric IgM is more efficient than other isotypes in binding antigens with many repeating epitopes like viral particles and RBCs due to its high valency.
- For example: the RBCs get clumped together into large aggregates when incubated with specific antibody in a process called agglutination.
- The same level of agglutination can be achieved by 100 to 1000 times more molecules of IgG than IgM.
- Viral particles also show similar phenomenon where less IgM is required in comparision to IgG to neutralize viral activity.
- Activation of complement is also effective or more efficient by IgM than IgG.
- The single molecule of pentameric IgM fulfills the requirement of at least two Fc regions in close proximity for complement activation.
- IgM has large size due to which it cannot diffuse well and for that reason it is present in less concentration in the intercellular tissue
- IgM binds to the receptors on secretory cells due to the presence of J chain.
- Due to this reason i.e. presence of J chain, it gets transported across the epithelial linings to enter the external secretions that bathe mucosal surfaces.
- IgM plays an important accessory role as a secretory immunoglobulin though the major isotype IgA is found in these secretions.
Immunoglobulin M (IgM): Structure and Properties