Explore chapters and articles related to this topic
The Inducible Defense System: Antibody Molecules and Antigen-Antibody Reactions
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
IgM has a molecular weight of 900,000 and is a pentamer of five subunits in a circular configuration joined by disulfide bridges (Figure 7.4). An additional polypeptide chain, called the J chain, helps stabilize the molecule. The J chain (M.W. 15,000 daltons) is coded for by a non-Ig gene. IgM is the largest molecule of any antibody of the five classes; because of its size, it circulates primarily in the vascular blood compartment. IgM is the first antibody to be made during a primary immune response. It is an efficient activator of the complement cascade, since only one bound IgM molecule is needed to lyse a cell. On the other hand, IgG requires two or more bound molecules to activate complement.
Immunoglobulins
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
Receptors for IgA Fc (FcαR) have been described on granulocytes and monocytes; IgM Fc receptors (FcμR) have been found on NK cells and some B cells; IgD Fc receptors (FcδR) have been described on some T cells. Immunoglobulin-binding factors for IgA, IgM and IgD have also been reported. The structures and distributions of these entities are not yet well-characterized. The poly-Ig receptor for J chain in polymeric immunoglobulin has been described above.
Immunoglobulins: Metabolism and biological properties
Published in Gabriel Virella, Medical Immunology, 2019
All polymeric immunoglobulins have one additional polypeptide chain, the J chain. This chain is synthesized by all plasma cells, including those that produce IgG. However, it is only incorporated to polymeric forms of IgM and IgA. It is thought that the J chain has some role in initiating polymerization. IgM proteins are assembled in two steps. First, the monomeric units are assembled. Then, five monomers and one J chain will be combined via covalent bonds to result in the final pentameric molecule. This assembly seems to coincide with secretion in some cells, in which only monomeric subunits are found intracellularly. However, in other cells, the pentameric forms can be found intracellularly and secretion seems linked to glycosylation.
Engineering a pure and stable heterodimeric IgA for the development of multispecific therapeutics
Published in mAbs, 2022
Florian Heinkel, Meghan M. Verstraete, Siran Cao, Janessa Li, Patrick Farber, Elizabeth Stangle, Begonia Silva-Moreno, Fangni Peng, Surjit Dixit, Martin J. Boulanger, Thomas Spreter Von Kreudenstein, Eric Escobar-Cabrera
Beyond greatly expanding the accessible formats and geometries of a monomeric antibody as has been seen for IgG,40 a heterodimeric IgA Fc also enables a new category of multispecific, multimeric monoclonal antibodies. One feature of IgA is that a higher valency is naturally accessible via J-chain-based multimers.17,32 These multivalent formats can provide avidity effects that increase apparent affinity of low-affinity paratopes and increase clustering and specificity for target cells with high receptor density.17,41 Furthermore, the presence of the J-chain enables covalent interaction of dimeric IgA with pIgR for transcytosis of the mucosa, leaving multimeric IgA bound to the secretory component.42 This feature of IgA could be used to direct a multispecific, multimeric antibody to mucosal environments following intravenous administration.43 Combining this higher valency with a heterodimeric IgA Fc gives rise to geometries and valencies of formats that were previously inaccessible and an opportunity to deliver multispecific IgA to mucosal environments (Figure 5).
Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants
Published in Gut Microbes, 2021
Audrey Y-H Teh, Lisa Cavacini, Yue Hu, Ozan S. Kumru, Jian Xiong, David T. Bolick, Sangeeta B. Joshi, Clemens Grünwald-Gruber, Friedrich Altmann, Mark Klempner, Richard L. Guerrant, David B. Volkin, Yang Wang, Julian K-C. Ma
A more comprehensive glycoanalysis was performed of the WT and ΔXF N. benthamiana produced SIgA1 and SIgA2 antibodies, using LC-ESI-MS. In this analysis, N-glycosylation sites on the alpha chains, J chain and secretory component were assessed quantitatively and individually as well as a potential O-glycosylation site on the alpha1 chain. Alpha1 heavy chains have two potential N-glycosylation sites and alpha2 heavy chains have four; J chain has one potential N-glycosylation site; and SC has five. The results were consistent with the findings from the Rapi-Fluor preliminary analysis. In addition, the analysis demonstrated that in the plant-produced SIgA1 antibodies, all potential N-glycosylation sites were occupied on the heavy and J chains, but no glycans could be detected associated with glycosites 1, 3 and 4 in secretory component (Suppl. Figure S2). Glycosite 2 on the alpha1 chain was ~30% non-glycosylated, suggesting reduced accessibility of this site, compared with glycosite 1. The major glycoforms are shown, with a preponderance of xylosylated (XA1) and xylosylated and fucosylated (FXA1, FXA2) glycoforms on the alpha chain and secretory component. In the ΔXF N. benthamiana produced antibodies, the results support the elimination of xylosylation and a significant knock-down of fucosylation.
Targeted IgMs agonize ocular targets with extended vitreal exposure
Published in mAbs, 2020
Yvonne Chen, Maciej Paluch, Julie A. Zorn, Sharmila Rajan, Brandon Leonard, Alberto Estevez, John Brady, Henry Chiu, Wilson Phung, Amin Famili, Minhong Yan, Claudio Ciferri, Marissa L. Matsumoto, Greg A. Lazar, Susan Crowell, Phil Hass, Nicholas J. Agard
To investigate the feasibility of applying IgMs to ocular targets we first sought to optimize their expression and purification. Expi293 cells were transiently transfected with various amounts of DNA encoding human IgM LC and HC with or without JC, supernatants were harvested, and LC-containing species were isolated by single-step purification off of a Capto L column. Isolated material was quantified and analyzed by size-exclusion chromatography (SEC) to estimate the various species present in the samples. Hexamer optimization proceeded by transfecting cells with plasmids containing LC and HC at a 1:1 or 2:1 ratio of plasmid DNA. Each ratio resulted in similar total protein yields (2.5–3 mg from a 30 ml expression) (Figure 1b), but product quality appeared improved at a 1:1 ratio, with reduced amounts of LC-dimer present (Figure 1c). Expression of putative pentamers was conducted by including J-chain in the transfection. The optimal ratio of 4:4:1 LC:HC:JC, maximized both expression and product quality (Figure 1b-c). Notably, the high level of LC and HC DNA relative to JC in the optimized conditions approximates the 10:10:1 chain ratio in the final IgM pentamer.