Question

IgM, unlike other heavy chain isotypes, appears in the serum as a pentamer of the basic four-chain Ig monomer; thus making it decavalent rather than bivalent in terms of combining sites. One intriguing result of this is an increase in the likelihood - all other things being equal - that the IgM will be bound (versus free). Another way of saying this is that even though the affinity constant (Ka) of each individual combining site is the same regardless of the overall molecule's valency, this decavalent version will have more whole Ig molecules bound (to antigen) at equilibrium than would a bivalent version (given equimolar levels of combining sites). This phenomenon is sometimes called increased "avidity" (to avoid using the rigorously defined chemical term "affinity" incorrectly). I'd like you to discuss a few issues raised by this:

• First, bearing in mind that IgM is the first isotype made during primary responses,why does this higher "avidity" make intuitive sense?
• Second, can you foresee ways that this added "stickiness" might also engender problems?
• Finally, does this mean that IgM molecules are more or less "specific" than their IgG counterparts? (watch it, that last one is tricky)

Answer 1

At the onset of a recent infection it is always the IgM antibodies that appear first. In fact this property of IgM being the primary response to any new infection is used as a serological tool to identify between current and old infections.

IgM circulates as a pentamer of disulfide-linked immunoglobulin molecules joined by a single cross-linking peptide called 'J ' Chain. Although the antibody binding affinity of monomeric (single) IgM is low, the multivalent structure of the molecule provides high pentameric antibody avidity. Hence with introduction of recent infection a high avidity of the molecule makes it more suitable to remove the intruder at the earliest and in a fastest possible way. The removal of intruding antigen, be it bacteria, virus or any other antigenic component is more important than making specific antibodies to the intruder.

Also, because of its huge molecular structure, restricts its distribution in the vascular component. Most evident that it can not cross the placental barrier and mother can only transfer IgG immunoglobulins to foetus. Hence, presence of IgM in foetal circulation indicates an infection (most likely viral) in the womb. This again has a diagnostic significance.

Also, althoigh IgM is decavalent, but while binding large antigenic molecules, ii only works as pentavalent, the five additional sites appearing as 'Blocked" due to steric hinderance. For many carbohydrate based antigens (as against most protein based antigens) Ig M is the only antibody response. IgG is not formed.

The IgG antibodies have a higher affinity for antigen than IgM whose affinity is more specifically called as Avidity, but when it comes to specificity to a particular antigen, they both are specific at the same level. In fact the higher affinity of IgG Molecules can at times create competition for getting at the antigen with IgM. But both are antigen specific.