Interests in the utility of non-IgG antibodies for therapeutic purposes have been increasing in the last few years. Especially, IgMs, which are complex molecules consisting of 10 (pentameric IgM) or 12 (hexameric IgM) combining sites, have attracted much attention. As an expert in the development of therapeutic non-IgG antibodies, Creative Biolabs has been focusing on the disease therapy research, development, and applications of IgM antibodies for years. We now proudly present our IgM glycoengineering services to facilitate your therapeutic IgM antibody development.
Introduction to IgM Antibody
Natural IgM is the major antibody produced in the primary immune response to foreign antigens. It exists in both membrane-associated form (i.e. on the surface of B cells as part of the B-cell receptor (BCR) complex) and secreted form. Secreted IgM is multimeric, consisting of five (pentameric) or six (hexameric) subunits, each of which consists of two heavy (μ) and two light chains (predominantly κ). The differences between these two types of IgM are that pentameric IgM has a single J chain, which is absent in hexameric IgM. The reasons that IgMs have begun to receive considerable attention as a therapeutic molecule ideal for specific clinical indications include but are not limited to:
- A significant degree of avidity for antigen due to the existence of 10 (or 12) binding units
- The ability to activate complement-dependent cytotoxicity effectively due to the abundance of Fc regions
- More efficient in binding to low abundant targets and cross-linking cell surface receptors
IgM Glycosylation Diversity
IgMs are highly glycosylated, with five N-linked glycosylation sites on each μ (heavy) chain and one present on the J chain. More specifically, the five N-glycans are attached to asparagine (Asn)-171, Asn-332, Asn-395, Asn-402, and Asn-563, while the single N-glycan on J chain is located at Asn-48. More importantly, glycosylation of human serum IgM is site-specific, with each of the five glycosylation sites having a different glycan profile. Sites 1-3 (Asn-171, Asn-332, and Asn-395) are dominated by fucosylated, monosialylated complex glycans, while sites 4 and 5 (Asn-402 and Asn-563) are comprised entirely of oligomannosidic structures. The J chain glycosylation site contains mainly sialylated bi-antennary glycans with or without core fucose.
Fig.1 N-glycosylation sites of IgM. (Arnold, 2007)
The Impact of Glycosylation on IgM Functions
The glycans at different IgM glycosylation sites have been reported to be associated with various biological functions, including B cell maturation (Asn-171), complement activation (Asn-402), and J-chain incorporation (Asn-563). Moreover, studies have also indicated that sialylation differences of N-linked glycans on IgM can influence the immunomodulatory effects of IgM on T cells. More specific functions of IgM glycosylation remain to be elucidated in the future.
IgM Glycoengineering Services Provided by Creative Biolabs
Antibodies of the IgM isotype are gaining in importance in the biological therapeutics industry, showing efficacy in infectious disease, inflammation, and cancer treatment. In view of the influence of IgM glycosylation on its biological properties and functions, Creative Biolabs now offers glycoengineering services for the expression of monoclonal IgM variants. With highly experienced scientists and high-end techniques, we can provide our clients with opportunities to investigate and manipulate the glycan compositions of IgMs, thereby improving their clinical efficacy.
Besides the IgM isotype, Creative Biolabs also offers glycoengineering services for other non-IgG antibodies, including IgA and IgE antibodies. For more detailed information, please feel free to contact us or directly send us an inquiry.
Reference
- Arnold, J.N.; et al. The Impact of Glycosylation on the Biological Function and Structure of Human Immunoglobulins. Annual Review of Immunology. 2007, 25(1): 21-50.
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