Epithelial cells are a source of natural IgM that contribute to innate immune responses

Shao, Wenwei; Hu, Fanlei; Ma, Jiamin; Zhang, Chi; Liao, Qinyuan; Zhu, Zhu; Liu, Enyang; Qiu, Xiaoyan

doi:10.1016/j.biocel.2016.01.017

Cited by 27 publications

(24 citation statements)

References 45 publications

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“…IgM molecule production per se is not restricted to B cells and lymphoid tissues; functional IgM secretion has been demonstrated in normal and malignant human epithelial cells , while the formation of immunoglobulins that arise de novo from ovarian tissue appears to be established . According to Jerne, “ Germ cells of an animal carry a set of v‐genes determining the combining sites of antibodies directed against a complete set of a certain class of histocompatibility antigens of the species to which this animal belongs ” .…”

Section: Discussionmentioning

confidence: 99%

“…While the naturally occurring immunoglobulin M (IgM) is permanently engaged in recognition and elimination of aberrant growth and cancerous tissue, the secretion of IgM molecules is not restricted to B cells but spontaneously occurs in murine and human normal and malignant epithelial cells as well. Moreover, although many anti‐glycan antibodies do not adhere to the paradigm of an adaptive immune response and are often referred to as “natural antibodies” , to date, based on the historical experiments of Springer et al.…”

Section: Introductionmentioning

confidence: 99%

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Early ovariectomy reveals the germline encoding of natural anti‐A‐ and Tn‐cross‐reactive immunoglobulin M (IgM) arising from developmental O‐GalNAc glycosylations. (Germline‐encoded natural anti‐A/Tn cross‐reactive IgM)

Arend

2017

Cancer Medicine

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While native blood group A‐like glycans have not been demonstrated in prokaryotic microorganisms as a source of human “natural” anti‐A isoagglutinin production, and metazoan eukaryotic N‐acetylgalactosamine O‐glycosylation of serine or threonine residues (O‐GalNAc‐Ser/Thr‐R) does not occur in bacteria, the O‐GalNAc glycan‐bearing ovarian glycolipids, discovered in C57BL/10 mice, are complementary to the syngeneic anti‐A‐reactive immunoglobulin M (IgM), which is not present in animals that have undergone ovariectomy prior to the onset of puberty. These mammalian ovarian glycolipids are complementary also to the anti‐A/Tn cross‐reactive Helix pomatia agglutinin (HPA), a molluscan defense protein, emerging from the coat proteins of fertilized eggs and reflecting the snail‐intrinsic, reversible O‐GalNAc glycosylations. The hexameric structure of this primitive invertebrate defense protein gives rise to speculation regarding an evolutionary relationship to the mammalian nonimmune, anti‐A‐reactive immunoglobulin M (IgM) molecule. Hypothetically, this molecule obtains its complementarity from the first step of protein glycosylations, initiated by GalNAc via reversible O‐linkages to peptides displaying Ser/Thr motifs, whereas the subsequent transferase depletion completes germ cell maturation and cell renewal, associated with loss of glycosidic bonds and release of O‐glycan‐depleted proteins, such as complementary IgM revealing the structure of the volatilely expressed “lost” glycan carrier through germline Ser residues. Consequently, the evolutionary/developmental first glycosylations of proteins appear metabolically related or identical to that of the mucin‐type, potentially “aberrant” monosaccharide GalNAcα1‐O‐Ser/Thr‐R, also referred to as the Tn (T “nouvelle”) antigen, and explain the anti‐Tn cross‐reactivity of human innate or “natural” anti‐A‐specific isoagglutinin and the pronounced occurrence of cross‐reactive anti‐Tn antibody in plasma from humans with histo‐blood group O. In fact, A‐allelic, phenotype‐specific GalNAc glycosylation of plasma proteins does not occur in human blood group O, affecting anti‐Tn antibody levels, which may function as a growth regulator that contributes to a potential survival advantage of this group in the overall risk of developing cancer when compared with non‐O blood groups.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Early ovariectomy reveals the germline encoding of natural anti‐A‐ and Tn‐cross‐reactive immunoglobulin M (IgM) arising from developmental O‐GalNAc glycosylations. (Germline‐encoded natural anti‐A/Tn cross‐reactive IgM)

Arend

2017

Cancer Medicine

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“…Humoral innate immunity, or the first line of defense, and its complex connection with ABO(H) phenotype formation are considered to play the main role in SARS-CoV-2 infection and in the course of subsequent disease. In contrast to adaptive, environmentally-induced immunoglobulin or B-cell activities, which are controlled by clonal selection, the production of the nonimmune and polyreactive IgM is not restricted to B cells, but spontaneously occurs in murine ( Zhou et al, 2011 , Shao et al, 2016 ) and human (F. Hu et al, 2012a ) normal and malignant epithelial cells as well. The early ovariectomy of the C57BL/10 inbred mouse ( Arend and Nijssen, 1976 , Arend and Nijssen, 1977a , Arend and Nijssen, 1977b ) may have revealed that in the mammalian species this IgM molecule is a germline-encoded antibody, which is, through a complex evolutionary process, structurally connected with the ancestral A-like/Tn antigen (detected in water-soluble ovarian glycolipids) and is considered its complementary protein (Arend, P, 2016; P., 2017).…”

Section: How the Abo(h) Blood Group Phenotype Might Dominate The Humomentioning

confidence: 99%

Why blood group A individuals are at risk whereas blood group O individuals are protected from SARS-CoV-2 (COVID-19) infection: A hypothesis regarding how the virus invades the human body via ABO(H) blood group-determining carbohydrates

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2021

Immunobiology

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“…Humoral innate immunity, or the first line of defense, and its complex connection with ABO(H) phenotype formation are considered to play the main role in SARS-CoV-2 infection and in the course of subsequent disease. In contrast to adaptive, environmentally-induced immunoglobulin or B-cell activities, which are controlled by clonal selection, the production of the nonimmune and polyreactive IgM is not restricted to B cells, but spontaneously occurs in murine (Zhou, O'Hara and Chen, 2011;Shao et al, 2016) and human (F. Hu et al, 2012a) normal and malignant epithelial cells as well. The early ovariectomy of the C57BL/10 inbred mouse (Arend and Nijssen, 1976;1977a;1977b) may have revealed that in the mammalian species this IgM molecule is a germline-encoded antibody, which is, through a complex evolutionary process, structurally connected with the ancestral Alike/Tn antigen (detected in water-soluble ovarian glycolipids) and is considered its complementary protein (Arend, P, 2016;P., 2017).…”

Section: How the Abo(h) Blood Group Phenotype Might Dominate The Humomentioning

confidence: 99%

Why Blood Group A Individuals Are at Risk Whereas Blood Group O Individuals Might Be Protected from SARS-CoV-2 (COVID-19) Infection: A Hypothesis Regarding How the Virus Invades the Human Body via Abo(H) Blood Group-Determining Carbohydrates

Arend¹

2020

Preprint

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While the angiotensin converting enzyme 2 (ACE2) protein is defined as the primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, the viral serine molecule might be mobilized by the host's transmembrane protease serine subtype 2 (TMPRSS2) enzyme from the viral spike (S) protein and hijack the host’s N-acetyl-D-galactosamine (GalNAc) metabolism. The resulting hybrid, serologically A-like/Tn (T-nouvelle) structure potentially acts as a host–pathogen functional molecular bridge. In humans, this intermediate structure will hypothetically be replaced by ABO(H) blood group-specific, mucin-type structures, in the case of infection hybrid epitopes, implicating the phenotypically glycosidic accommodation of plasma proteins. The virus may, by mimicking the synthetic pathways of the ABO(H) blood groups, bind to the cell surfaces of the blood group O(H) by formation of a hybrid H-type antigen as the potential precursor of hybrid non-O blood groups, which does not affect the highly anti-glycan aggressive anti-A and anti-B isoagglutinin activities, exerted by the germline-encoded nonimmune immunoglobulin M (IgM). In the non-O blood groups, which have developed from the H-type antigen, these IgM activities are downregulated by phenotypic glycosylation, while adaptive immunoglobulins might arise in response to the hybrid A and B blood group structures, suggesting the exertion of autoreactivity. The non-O blood groups thus become a preferred target for the virus, whereas blood group O(H) individuals, lacking the A/B phenotype-determining enzymes and binding the virus alone by hybrid H-type antigen formation, have the least molecular contact with the virus and maintain the critical anti-A and anti-B isoagglutinin activities, exerted by the ancestral IgM, which is considered the humoral spearhead of innate immunity.

show abstract

Epithelial cells are a source of natural IgM that contribute to innate immune responses

Cited by 27 publications

References 45 publications

Early ovariectomy reveals the germline encoding of natural anti‐A‐ and Tn‐cross‐reactive immunoglobulin M (IgM) arising from developmental O‐GalNAc glycosylations. (Germline‐encoded natural anti‐A/Tn cross‐reactive IgM)

Early ovariectomy reveals the germline encoding of natural anti‐A‐ and Tn‐cross‐reactive immunoglobulin M (IgM) arising from developmental O‐GalNAc glycosylations. (Germline‐encoded natural anti‐A/Tn cross‐reactive IgM)

Why blood group A individuals are at risk whereas blood group O individuals are protected from SARS-CoV-2 (COVID-19) infection: A hypothesis regarding how the virus invades the human body via ABO(H) blood group-determining carbohydrates

Why Blood Group A Individuals Are at Risk Whereas Blood Group O Individuals Might Be Protected from SARS-CoV-2 (COVID-19) Infection: A Hypothesis Regarding How the Virus Invades the Human Body via Abo(H) Blood Group-Determining Carbohydrates

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