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Immunoglobulin M (IgM) is the second most common antibody in humans surpassed only by immunoglobulin G (IgG). The IgM molecule is a pentamer – whereas IgG is a dimer – and with a molecular weight of appr. 900,000 D IgM has more than 5 times the molecular weight of IgG. In the antibody-mediated immunity, IgM is an earlier responder that appears soon after initial exposure to antigen. Due to its pentamer structure IgM has high avidity even for weak antigens and binds them very effectively. Another notable property of IgM is its very high ability of bind complement.

While IgM plays an important role in the immune response to infectious agents, the use of IgM in biomedicine has been limited. This is in part due to real and perceived challenges in working with mouse or human IgM, and possibly also due to the stupendous success of IgGs – both as reagents and therapeutics- which has left limited space for the exploration of IgM. However, there remains interest in IgM for the treatment of autoimmune disease and to prevent virus infection.

There are some challenges in developing processes for IgM. For example, IgM is not as soluble as other plasma proteins. In practical terms, the solubility of IgM limits its final concentration to about 15mg/ml, whereas IgG can be routinely concentrated to 30mg/ml and some IgGs can reach 200mg/ml. But there are also perceived challenges that are not huge obstacles. For example, while IgMs are large proteins, the size of the IgM molecule in solution (Stokes radius) is only about 50% larger than that of IgG, meaning that IgM and IgG behave very similar with regard to purification by ultrafiltration. Furthermore, while IgGs are easily purified by affinity chromatography using Protein A, IgM does not bind to Protein A or Protein G. However, chromatography of IgM is only “difficult” compared to IgG, it is “easy” compared to most other recombinant proteins. There are decent affinity resins commercially available that can be used for the screening of IgM candidates, and for the manufacturing setting the fact that IgM binds well to cationic as well as anionic exchangers can be readily exploited.

Need help working with IgM? Somatek has developed and implemented processes that result in high-yield, pure, concentrated IgM preparations that retain full biological function. For your consideration please see this example. http://www.bio-rad.com/webroot/web/pdf/lsr/literature/Bulletin_1917.pdf