PHENO4444Neu.pdf (1.04 MB)
ABO phenotype and innate isoagglutinin specificities as they arise from “glycosidic exclusion” and relate to human reproduction. A hypothesis*
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journal contribution
posted on 2016-12-30, 08:59 authored by Peter ArendPeter ArendThe phenotypes of the human histo
(blood) group) ABO system and its innate
isoagglutinin specificities arise apparently in a process, which may be called
“glycosidic exclusion”, i.e. a physiological
principle, where in normal conditions the simultaneous appearance of a
phenotype and its corresponding innate (auto) antibody is reduced or excluded
by identical glycosylations of complementary domains on cell surfaces and
plasma proteins involving those of the neonatal IgM. In view of the fundamental
O-glycan emptiness of the circulating
IgM molecule, its distinct N/O-glycan
complementarity in the human phenotype O might, together with “open” glycosidic
sites at the ABO-convertible, classic
blood group O RBC surface, suggest a transient expression of an ancestral glycan, which has been "lost"
over the course of maturation and released its complementary protein into the
circulation. In fact, the mammalian non-somatic, embryogenic stem cell (ESC)-germ
cell (GC) transformation is characterized by a transient, immature O-GalNAc glycan expression, identified
potentially in growth-dependent, blood group A-like GalNAc glycan-bearing,
ovarian polar glycolipids of the C57/BL/10 mouse, while the syngeneic complementary
anti-A reactive IgM does not appear in early ovariectomized animals. This non-somatically
encoded IgM molecule emerging from developmental glycan depletion, which has
completed germ cell maturation and/or cell renewal processes, should reflect a
genetic history disclosed over the course of haploidizations or chromosomal
rearrangements and has not undergone clonal selection. Consequently, it
primarily does not differentiate between self and non-self and might, due to “open”
glycosidic sites, suggest enzyme-substrate
competition with subsequent, yet non-somatic glycosylations in the ongoing
ESC-GC transformations and affecting GC maturation. However, the
membrane-bound somatic N- and O-glycotransferases, which initiate, after formation of the zygote,
the complex construction of the human ABO phenotypes in
the trans cisternae of the Golgi apparatus, are associated and/or
completed with soluble enzyme versions exerting identical specificities in
plasma and competing vice versa by glycosylation of neonatal IgM amino
acids, where they suggest to accomplish the clearance of anti-A autoreactivity
at GalNAc-complementary domains. Sustaining the
lineage-maintaining position of the A allele, the discovery of OA hybrid alleles at the normal ABO locus and in heterozygous ESC lines
have, together with clinical observations, raised discussions about a silent
A-allelic support within blood group O reproductions. The question arising
therewith of whether a fictional “continued blood group O inbreeding” ultimately
occurs without silent A-allelic functions remains unanswered because the
genetic relationship between non-somatic GalNAc-glycosylations that operate
before sperm-egg recognition and somatic GalNAc-glycosylations
occurring after the formation of the zygote have to be elucidated.
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