Immunoglobulin M: An Ancient Antiviral Weapon – Rediscovered

Gong, Siqi; Ruprecht, Ruth M.

doi:10.3389/fimmu.2020.01943

Cited by 64 publications

(59 citation statements)

References 81 publications

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“…By contrast, adaptive IgM antibodies are produced by post-germinal center plasma cells and memory B cells, so they have highly mutated V regions [ 59 , 134 , 135 ]. Although each natural IgM monomer has relatively low affinity to antigens as it normally does not undergo somatic hypermutation and affinity maturation, the presence of multivalent antigen-binding sites in IgM pentamers or hexamers confers high avidity, which is pivotal in the capacity of IgM for agglutinating pathogens by binding to specific antigenic motifs [ 101 , 136 ]. IgM exerts its functions primarily by fixing complement C1q, activating complement-dependent cytotoxicity and facilitating IgG-mediated opsonization [ 137 ].…”

Section: Joining Chain (J Chain)mentioning

confidence: 99%

Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis

Hao

Wang

2021

IJMS

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Transcytosis of polymeric IgA and IgM from the basolateral surface to the apical side of the epithelium and subsequent secretion into mucosal fluids are mediated by the polymeric immunoglobulin receptor (pIgR). Secreted IgA and IgM have vital roles in mucosal immunity in response to pathogenic infections. Binding and recognition of polymeric IgA and IgM by pIgR require the joining chain (J chain), a small protein essential in the formation and stabilization of polymeric Ig structures. Recent studies have identified marginal zone B and B1 cell-specific protein (MZB1) as a novel regulator of polymeric IgA and IgM formation. MZB1 might facilitate IgA and IgM transcytosis by promoting the binding of J chain to Ig. In this review, we discuss the roles of pIgR in transcytosis of IgA and IgM, the roles of J chain in the formation of polymeric IgA and IgM and recognition by pIgR, and focus particularly on recent progress in understanding the roles of MZB1, a molecular chaperone protein.

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Section: Joining Chain (J Chain)mentioning

confidence: 99%

Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis

Hao

Wang

2021

IJMS

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“…IgM is the first responder to foreign invaders including the viruses that have caused major pandemics, such as the current COVID-19 virus. IgM, considered an ancient antiviral weapon, exists in all vertebrates ( 220 ). Its monomeric form ( Figure 8 ) is expressed on B cells as the B-cell antigen receptor ( 220 ).…”

Section: Igm Pattern Recognition Protein Innate Immune Responses and The Coronavirusmentioning

confidence: 99%

“…IgM, considered an ancient antiviral weapon, exists in all vertebrates ( 220 ). Its monomeric form ( Figure 8 ) is expressed on B cells as the B-cell antigen receptor ( 220 ). IgM is secreted mainly as a pentameric molecule ( Figure 8 ) ( 220 , 221 ) containing a joining chain (J chain), and in humans has a high serum concentration (1.5 mg/ml).…”

Section: Igm Pattern Recognition Protein Innate Immune Responses and The Coronavirusmentioning

confidence: 99%

Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

Labarrere

Kassab

2021

Front. Immunol.

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The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host’s immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host’s innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of the pattern recognition protein (PRP) trident composed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.

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“…As a result of recent technical advances in structural biology, IgM has received a significant revision in terms of its structure (see reviews [6,13,41]). IgM was traditionally considered as a symmetrical pentamer like a planar star-shaped pentagon, with the Fab fragments pointing away from the inner core of the Fc regions.…”

Section: Recent Structural Aspects Of Igm Ligandmentioning

confidence: 99%

Differences between Human and Mouse IgM Fc Receptor (FcµR)

Kubagawa

Skopnik

Al-Qaisi

et al. 2021

IJMS

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Both non-immune “natural” and antigen-induced “immune” IgM are important for protection against pathogens and for regulation of immune responses to self-antigens. Since the bona fide IgM Fc receptor (FcµR) was identified in humans by a functional cloning strategy in 2009, the roles of FcµR in these IgM effector functions have begun to be explored. In this short essay, we describe the differences between human and mouse FcµRs in terms of their identification processes, cellular distributions and ligand binding activities with emphasis on our recent findings from the mutational analysis of human FcµR. We have identified at least three sites of human FcµR, i.e., Asn66 in the CDR2, Lys79 to Arg83 in the DE loop and Asn109 in the CDR3, responsible for its constitutive IgM-ligand binding. Results of computational structural modeling analysis are consistent with these mutational data and a model of the ligand binding, Ig-like domain of human FcµR is proposed. Serendipitously, substitution of Glu41 and Met42 in the CDR1 of human FcµR with mouse equivalents Gln and Leu, either single or more prominently in combination, enhances both the receptor expression and IgM binding. These findings would help in the future development of preventive and therapeutic interventions targeting FcµR.

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Immunoglobulin M: An Ancient Antiviral Weapon – Rediscovered

Cited by 64 publications

References 81 publications

Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis

Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis

Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

Differences between Human and Mouse IgM Fc Receptor (FcµR)

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