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

Peter Arend
2016 Figshare  
While eukaryotic 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 puberty. These murine ovarian glycolipids are also complementary to the Helix pomatia agglutinin, which has emerged from the protein coats of fertilized eggs of the snail and thus
more » ... snail and thus reveals the presence of functional snail O-GalNAc glycans.The hexameric structure of this lower eukaryotic, Helix pomatia agglutinin suggests evolutionary relationship to the mammalian non-immune 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.
doi:10.6084/m9.figshare.1279394.v334 fatcat:p555ir3rrzbwnlzw327tekozri