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IgA: Structure, Function, and Developability
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Structure, Function, and Therapeutic Use of IgM Antibodies

IGM Biosciences Inc, 325 East Middlefield Road, Mountain View, CA 94043, USA
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Antibodies 2020, 9(4), 53; https://doi.org/10.3390/antib9040053
Received: 16 September 2020 / Accepted: 9 October 2020 / Published: 13 October 2020
(This article belongs to the Special Issue Structure and Function of Antibodies)
Natural immunoglobulin M (IgM) antibodies are pentameric or hexameric macro-immunoglobulins and have been highly conserved during evolution. IgMs are initially expressed during B cell ontogeny and are the first antibodies secreted following exposure to foreign antigens. The IgM multimer has either 10 (pentamer) or 12 (hexamer) antigen binding domains consisting of paired µ heavy chains with four constant domains, each with a single variable domain, paired with a corresponding light chain. Although the antigen binding affinities of natural IgM antibodies are typically lower than IgG, their polyvalency allows for high avidity binding and efficient engagement of complement to induce complement-dependent cell lysis. The high avidity of IgM antibodies renders them particularly efficient at binding antigens present at low levels, and non-protein antigens, for example, carbohydrates or lipids present on microbial surfaces. Pentameric IgM antibodies also contain a joining (J) chain that stabilizes the pentameric structure and enables binding to several receptors. One such receptor, the polymeric immunoglobulin receptor (pIgR), is responsible for transcytosis from the vasculature to the mucosal surfaces of the lung and gastrointestinal tract. Several naturally occurring IgM antibodies have been explored as therapeutics in clinical trials, and a new class of molecules, engineered IgM antibodies with enhanced binding and/or additional functional properties are being evaluated in humans. Here, we review the considerable progress that has been made regarding the understanding of biology, structure, function, manufacturing, and therapeutic potential of IgM antibodies since their discovery more than 80 years ago. View Full-Text
Keywords: IgM (immunoglobulin M); hexameric; pentameric; polymeric; polyvalency; joining chain (J-chain); avidity; complement dependent cytotoxicity (CDC); poly Ig receptor (pIgR) IgM (immunoglobulin M); hexameric; pentameric; polymeric; polyvalency; joining chain (J-chain); avidity; complement dependent cytotoxicity (CDC); poly Ig receptor (pIgR)
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MDPI and ACS Style

Keyt, B.A.; Baliga, R.; Sinclair, A.M.; Carroll, S.F.; Peterson, M.S. Structure, Function, and Therapeutic Use of IgM Antibodies. Antibodies 2020, 9, 53. https://doi.org/10.3390/antib9040053

AMA Style

Keyt BA, Baliga R, Sinclair AM, Carroll SF, Peterson MS. Structure, Function, and Therapeutic Use of IgM Antibodies. Antibodies. 2020; 9(4):53. https://doi.org/10.3390/antib9040053

Chicago/Turabian Style

Keyt, Bruce A., Ramesh Baliga, Angus M. Sinclair, Stephen F. Carroll, and Marvin S. Peterson. 2020. "Structure, Function, and Therapeutic Use of IgM Antibodies" Antibodies 9, no. 4: 53. https://doi.org/10.3390/antib9040053

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