While as a source of the human anti-A/B isoagglutinin production neither N- nor O-linked N-acetyl-D-galactosamine (D-GalNAc)-determined, native blood group A-like specificities have yet been demonstrated in prokaryotic microorganisms, the O-GalNAc glycan-bearing ovarian glycolipids, discovered in C57BL/10 mice, are complementary to the syngeneic anti-A-reactive, secretory immunoglobulin M (IgM), which does not appear in animals subjected to an ovariectomy prior to the onset of puberty. This

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... ne anti-A "auto" antibody and the human innate or non-immune anti-A isoagglutinin show identical serological reaction patterns. In mouse and man, this molecule most likely gets its complementary footprints from the early growth-dependent, trans-species O-GalNAc glycosylation of proteins and subsequent GalNAc transferase depletion that completes the cell differentiation processes and results in release of complementary protein(s) involving the secretory IgM, which might establish this mechanism through expression of germline-specific serine residues and reveals the structure of the volatilely expressed, "lost" glycan. These early or first O-GalNAc glycosylations of proteins appear metabolically related to those of the mucin-type, "aberrant" monosaccharide GalNAcα1-O-Ser/Thr-R or Tn antigen and explain the anti-Tn cross-reactivity of anti-A-specific immunoglobulins and pronounced occurrence of cross-reactive anti-Tn antibody in the plasma of human histo (blood) group O. In fact, in the human blood group O, an A-allelic, phenotype-specific GalNAc glycosylation of plasma proteins does not occur and affect the levels of the anti-Tn antibody, which may function as a growth regulator that depending on its levels, initiates the process of growth inhibition through enzyme-substrate competition with subsequent trans-species O-GalNAc-glycosylations and mediates autologous cellular cytotoxicity.