Natural anti-A and Tn-cross-reactive IgM arise from developmental O-GalNAc glycosylations.*
release_5z4rv4dm2vau5ngry2bnzlqdgu
by
Peter Arend
2016
Abstract
While native blood group A-like glycans have not been
demonstrated in prokaryotic microorganisms as a source of human "natural"
anti-A/B isoagglutinin production and the trans-species, vertebrate <i>O</i>-GalNAc-Ser/Thr glycosylations do not
occur in bacteria, the <i>O</i>-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. This murine anti-A "auto" antibody, which is
distinct from adaptive, cross-reactive anti-A/B reactivities, and the human
innate anti-A isoagglutinin show identical serological reaction patterns. In mouse
and man, this non-immune antibody molecule most likely obtains its
complementarity from the early trans-species <i>O</i>-GalNAc glycosylation of
proteins and subsequent GalNAc transferase depletion, which completes the cell
differentiation processes and causes the release of characteristic <i>O</i>-glycan-depleted, complementary
proteins, such as secretory IgM, which might reveal the structure of the
volatilely expressed, "lost" glycan through germline-specific serine residues.
Consequently, the early or first <i>O</i>-GalNAc glycosylations of proteins
appear metabolically related to those of the mucin-type, "aberrant"
monosaccharide GalNAcα1-<i>O</i>-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 <i>O</i>-GalNAc-glycosylations.
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Date 2016-11-10
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