While native blood group A-like glycans have not been demonstrated in prokaryotic microorganisms as a source of human "natural" anti-A/B isoagglutinin production and the trans-species, vertebrate O-GalNAc-Ser/Thr glycosylations do 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 does not appear in animals that have undergone ovariectomy prior to the onset of

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... y. This murine anti-A "auto" antibody, which is distinct from adaptive, cross-reactive anti-A/B reactivities, and the human innate anti-A isoagglutinin show identical serological reaction patterns. In mouse and man, this non-immune antibody molecule most likely obtains its complementarity from the early trans-species O-GalNAc glycosylation of proteins and subsequent GalNAc transferase depletion, which completes the cell differentiation processes and causes the release of characteristic O-glycan-depleted, complementary proteins, such as secretory IgM, which might reveal the structure of the volatilely expressed, "lost" glycan 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.