@article{arend_2016,
title={Natural anti-A and Tn-cross-reactive IgM arise from developmental O-GalNAc glycosylations.*},
DOI={10.6084/m9.figshare.1279394.v334},
abstractNote={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 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.},
publisher={Figshare},
author={Arend, Peter},
year={2016},
month={Dec}
}