IgM Antibody

Immunoglobulin M (IgM) is the primary natural antibody in the innate immune system, initially expressed during B cell development in response to foreign pathogens. IgM is a macro-immunoglobulin secreted in the form of pentamers or hexamers. Pentameric IgM contains 10 antigen-binding domains, while hexameric IgM contains 12, enabling efficient engagement and high avidity binding to antigens.

IgM Antibody Structure

Unlike IgG, IgM antibodies exist in various structural forms, such as monomers, pentamers (with a J chain), and hexamers (without a J chain). Monomeric IgM is a heterotetramer with a molecular weight of 180 kDa. Pentameric IgM, which is the predominant form of secreted IgM (sIgM), has a molecular weight of over 900 kDa. The assembly of pentameric IgM depends on the Joining (J) chain, a small 15 kDa glycoprotein. This pentameric structure is stabilized by disulfide bonds between the J chain and the Fc regions of IgMs. In human tissues, the J chain protects sIgM from proteases and facilitates immunoglobulin transport, providing immune protection.

Fig. 1 The structure of membrane bound IgM (mIgM) and secreted IgM (sIgM).^{1, 2}

IgM Antibody Function

IgM has a half-life of 5 to 10 days in serum. It primarily acts as a potent activator of the classical complement pathway by binding Fc portions to C1q. A single pentameric IgM can sufficiently facilitate rapid complement activation due to its five different Fc domains. As a powerful activator of complement, IgM plays a crucial role in eradicating encapsulated bacteria, destroying pathogens, promoting inflammation, and facilitating opsonization.

Fig. 2 Secreted IgM is essential in infections and non-communicable diseases.^{1, 2}

IgM Antibody Applications

IgM antibodies recognize various pathogenic antigens and mediate immune responses. Many diseases are associated with elevated IgM levels, IgM deficiency, or autoimmune responses mediated by IgM. These antibodies have potential applications in antibody drug discovery:

• IgM antibodies have demonstrated efficacy in various animal models.
• IgM antibodies against tumor antigens have been evaluated in clinical trials.
• The flexibility of IgM in binding multiple targets on the cell surface makes it an ideal platform for developing agonists.
• IgM-mediated autoimmunity can be utilized to ameliorate graft rejections during transplantation procedures.

IgM Antibody Production and Purification

Compared to IgG antibodies, IgMs do not bind well to protein A or G resins. IgM antibodies are sensitive to pH conditions and are soluble within narrow solubility ranges. Their large molecular size also reduces their diffusion constant relative to IgG. However, IgMs have high charge, making ion exchange (IEX) more suitable for their purification. High-purity IgM fragments can be obtained by controlling flow rates and adjusting salt concentrations. Creative Biolabs has extensive experience in IgM manufacturing and recombinant IgM expression. We offer custom IgM antibody services and products to support your drug discovery research.

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For Research Use Only. Not For Clinical Use.