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

Peter Arend
2016 Figshare  
While neither N- nor O-linked N-acetyl-D-galactosamine (D-GalNAc)-determined, native blood group A-like glycans have yet been demonstrated in prokaryotic microorganisms as a source of the human "natural" anti-A/B isoagglutinin production, the O-linked 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 that underwent ovariectomy prior to the onset of
more » ... he onset of puberty. This murine anti-A "auto" antibody and the human innate or non-immune anti-A isoagglutinin show identical serological reaction patterns. In mouse and man, this antibody molecule most likely 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 results in the release of O-glycan-depleted, complementary protein(s). This mechanism of IgM formation might be established through expression of germline-specific serine residues that reveal the structure of the volatilely expressed, "lost" glycan. 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 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 of 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, impacting the levels of the anti-Tn antibody, which may function as a growth regulator that depending on its levels, may initiate a complex process of growth inhibition through enzyme-substrate competition with subsequent trans-species O-GalNAc-glycosylations.
doi:10.6084/m9.figshare.1279394.v322 fatcat:jxw7zuecinhf7hpq4qkusggpma