Natural anti-A and Tn-cross-reactive IgM arise from developmental O-GalNAc glycosylations.* release_p555ir3rrzbwnlzw327tekozri

Abstract

While eukaryotic <i>O</i>-GalNAc-Ser/Thr glycosylations do not occur in bacteria, the <i>O</i>-GalNAc glycan-bearing ovarian glycolipids, discovered in C57BL/10 mice, are complementary to the syngeneic, anti-A-reactive immunoglobulin M (IgM), which does not appear in animals that have undergone ovariectomy prior to the onset of puberty. These murine ovarian glycolipids are also complementary to the <i>Helix pomatia</i> agglutinin, which has emerged from the protein coats of fertilized eggs of the snail and thus reveals the presence of functional snail <i>O</i>-GalNAc glycans.The hexameric structure of this lower eukaryotic, <i>Helix pomatia</i> agglutinin suggests evolutionary relationship to the mammalian non-immune IgM molecule, which hypothetically obtains its complementarity from the early trans-species <i>O</i>-GalNAc glycosylation of proteins and subsequent GalNAc transferase depletion that completes the cell differentiation processes and causes the release of <i>O</i>-glycan-depleted, complementary proteins, such as secretory IgM revealing the structure of the volatilely expressed, "lost" glycan carrier through germline-specific serine residues. Consequently, the early or first <i>O</i>-GalNAc glycosylations of proteins appear metabolically related to those of the mucin-type, "aberrant" monosaccharide GalNAcα1-<i>O</i>-Ser/Thr-R, also referred to as the Tn antigen, and explain the anti-Tn cross-reactivity of anti-A-specific immunoglobulins and the pronounced occurrence of cross-reactive anti-Tn antibody in plasma from humans with histo (blood) group O. In fact, in human blood group O, A-allelic, phenotype-specific GalNAc glycosylation of plasma proteins does not occur, affecting the levels of the anti-Tn antibody, which may function as a growth regulator that, depending on its levels, initiates a complex process of growth inhibition through enzyme-substrate competition with subsequent trans-species <i>O</i>-GalNAc-glycosylations.
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