IgM Antibody

IgM Antibody Production and Characteristics

The first antibodies to be produced during a humoral immune response are always IgM. This is because the VDJ joining gene rearrangement method, occurs just 5' prime to the Constant, Cmu, region gene exons. Moreover, these primary early IgM are produced prior to any somatic hypermutation and are therefore of low affinity, but IgM antibodies are capable of forming pentamers, with a valence of 10 (also hexamers), capable of binding simultaneously to multivalent antigens, compensating for the low affinity of the monomers through high avidity (therefore, binds many antigens, increasing complement initiation efficiency). However, due to the large size of the IgM pentamers, they are usually confined to the blood and are highly potent in activating the complement system. IgM is valuable as the initial antibody produced because it can be rapidly produced and highly potent in activating complement, allowing for the control and clearance of bloodstream infections before they begin to spread. Upond binding to the surface of a pathogen, IgM deforms the pentamer into a staple form, which exposes the binding sites for the C1q heads. C1q binds, though with low affinity to IgG (some subclasses), only when a single C1q can interact with two or more IgG molecules, that are held through binding antigen within 30-40 nm of one another. Thereofre, this requires the binding of many IgG molecules to a single pathogen, depicting that IgM is more efficient in activating complement than IgG (IgM exists as a multimer). In addition, IgM is often produced also in subsequent responses, including secondary responses and after somatic hypermutation (1).

The functional characteristics of IgM are a result of its diverse structure. IgM antibody monomers lack a hinge region but contain an extra heavy-chain domain that replaces the lacking hinge region. Moreover, IgM can form multimers, due to the C region containing a tailpiece of 18 amino acids that contain a cysteine residue essential for polymerization, found only on the secreted forms of IgM (like IgA). In addition, a separate 15 kDa polypeptide chain called the J chain promotes polymerization by linking the above mentioned cysteines of the tailpiece. In pentameric IgM, the monomers are crosslinked by disulfide bonds to one another and to the J chain. IgM can also form hexamers that lack a J chain. However, these hexamers are more efficient in complement activation (1).

References:

1. Janeway C.A., Travers P., Walport M., and Capra J.D. 1999. Immunobiology: The immune system in health and disease. Garland Publishing, 4th ed., New York, USA pages 1-40, 2.5-2.22, 3.1-3.12

2. Delves P., and Roitt I. 1999. Encyclopedia of Immunology. Academic Press Inc., 2nd ed., San Diego, USA

3. 1994 Current Protocols in Molecular Biology. Volume 2. John Wiley & Sons Inc., USA

4. Cruse J., and Lewis R. 1995. Illustrated Dictionary of Immunology. CRC Press Inc., USA pages 1960-1965

5. Chen F.H., and Painter R.H. 1997. Domain switched mouse IgM. IgG2b hybrids indicate individual roles for C domains in the regulation of the interactions of IgM complement C1q. J. Immunol. 159, 3354-3363