Germline encoded anti-A-reactive IgM arising from growth-dependent and aberrant O-GalNAc glycosylations.* [article]

Peter Arend
2016 Figshare  
While O-linked GalNAc glycosylated structures do not occur in plants, the germline encoding of an anti-A-reactive immunoglobulin M (IgM) molecule that is complementary to mammalian O-GalNAc glycan-bearing ovarian glycolipids, was experimentally documented in C57BL/10 mice. This anti-A antibody, which does not appear in animals subjected to an ovariectomy prior to the onset of puberty, appears serologically identical to the human innate anti-A isoagglutinin. The target of this antibody is a
more » ... -species developmental antigen that signifies malignancy when accumulating in non-developmental tissues. 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.
doi:10.6084/m9.figshare.1279394.v291 fatcat:j4a335zhdjbsdeyxc6wuq57pzi