![]() In the plasma of humans and mice, the pentameric form is the most abundant IgM version. Multiple IgM monomers assemble through interchain disulfide bridge formation between cysteines in the Cμ2, Cμ3, and the tailpiece to form polymeric IgM. However, monomeric IgM is frequently secreted in patients with autoimmune diseases ( 6, 7). When secreted, IgMs are predominantly polymers in healthy individuals. Monomeric IgM is mostly expressed as a surface-bound receptor on B cells, and it is essential for B-cell development. However, the lack of a hinge region does not imply that IgM molecules lack flexibility ( 5). The Cμ2 domain in the μ chain replaces the hinge region found in the heavy chains of IgG, IgD, and IgA that provides rotational flexibility of the fragment antigen-binding (Fab) domains in these heavy chains ( 4). ![]() The μ chain constant region contains four domains (Cμ1-Cμ2-Cμ3-Cμ4) and a C-terminal tailpiece ( Figure 1A). Monomeric IgM consists of two heavy (μ) and two light (L) chains, like monomers of all other antibody classes. The goal of this review is to give an overview of recent data regarding IgM structure, function, and IgM’s role in acute and longer-lasting antiviral host defenses against virus acquisition. However, despite IgM’s unique characteristics, its role in the prevention and treatment of viral infections remains understudied. IgM is also a potent complement activator. The high avidity may also allow IgM to better tolerate mutations in viral targets – an important consideration for viral pathogens with high mutation rates. ![]() ![]() IgM’s multimeric structure is well suited to bind viral surface proteins. Consequently, viral infections of the fetus or newborn are recognized by IgM responses against the background of transplacentally transferred maternal IgG. IgM’s pentameric structure prevents passage across the placenta. The J chain allows IgM to be transported across mucosal epithelia through binding with the polymeric immunoglobulin receptor (pIgR), an interaction that leads to the formation of secretory IgM ( 3).īecause IgM is the first antibody response in viral infections, this Ig class has important value for diagnosis. In humans, IgM is present at a relatively high concentration in serum (∼1.47 mg/ml) ( 2). When secreted, IgM is predominantly pentameric and contains the joining chain (J chain). Its monomeric form is expressed on B cells as the B-cell antigen receptor. It is the only antibody class that exists in all vertebrate animals ( 1). Immunoglobulin M (IgM) is the first responder to foreign invaders – including viral pathogens that cause major pandemics. ![]() Together, new data on IgM function raise the possibility that vaccine strategies aimed at preventing virus acquisition could include this ancient weapon. Importantly, such long-lived IgM plasma cells had been induced by immunization 1 year before challenge. In fact, IgM produced by such cells contained somatic hypermutations and was linked to protection against lethal influenza virus challenge in murine models. Finally, IgM’s role in adaptive immunity goes beyond being only a first defender to respond to pathogen invasion, as long-lived IgM plasma cells have been observed predominantly residing in the spleen. Third, recombinant IgM delivered mucosally by passive immunization gave proof-of-concept that this antibody class can prevent mucosal simian-human immunodeficiency virus transmission in non-human primates. Second, this gap allows IgM to serve as carrier of a specific host protein, apoptosis inhibitor of macrophages (AIM), which is released to promote removal of dead-cell debris, cancer cells, or pathogens. First, IgM – long thought to be a perfect pentamer – was shown to be asymmetric, resembling a quasi-hexamer missing one monomer and containing a gap. Recent discoveries have shed new light onto immunoglobulin M (IgM), an ancient antibody class preserved throughout evolution in all vertebrates.
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