When the O-GalNAc glycan-bearing ovarian glycolipids, discovered in the C57BL/10 mouse, are complementary to its syngeneic, anti-A-reactive immunoglobulin M (IgM), which does not appear in animals that have undergone ovariectomy prior to the onset of puberty, these mammalian ovarian glycolipids are also complementary to the anti-A/Tn cross-reactive Helix pomatia agglutinin, a molluscan defense protein, which has emerged from the egg coats of the snail and reveals its recently discovered

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... glycan. The hexameric structure of this primitive, invertebrate defense protein suggests an evolutionary relationship to the non-immune, mammalian defense protein or ancestral IgM molecule, which hypothetically obtains its complementarity from the early trans-species O-GalNAc glycosylation of proteins and subsequent GalNAc transferase depletion that completes the cell differentiation processes and causes the release of O-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 O-GalNAc glycosylations of proteins appear metabolically related to those of the mucin-type, "aberrant" monosaccharide GalNAcα1-O-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 O-GalNAc-glycosylations.