ABO phenotype and innate isoagglutinin specificities as they arise from “glycosidic exclusion” and relate to human reproduction. A hypothesis*
Creators: name: Arend, Peter
Publisher: name: figshare
Year: 2016
Subjects: subject: Hematology
subject: Botany
subject: Cancer
subject: Developmental Biology
subject: Immunology
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: Biotechnology
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Anatomy
subject: Evolutionary Biology

description: The phenotypes of the human histo (blood) group) A<i>B</i>O system and its innate isoagglutinin specificities arise apparently in a process, which may be called “glycosidic exclusion”, <i>i.e.</i> 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 <i>O</i>-glycan emptiness of the circulating IgM molecule, its distinct <i>N/O</i>-glycan complementarity in the human phenotype O might, together with “open” glycosidic sites at the A<i>B</i>O-convertible, classic blood group O RBC surface, suggest a transient expression of an ancestral<i> </i>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 <i>O</i>-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. <sub> </sub>However, the membrane-bound somatic <i>N</i>- and <i>O</i>-glycotransferases, which initiate, after formation of the zygote, the complex construction of the human A<i>B</i>O phenotypes in the trans cisternae of the <em>Golgi apparatus, are associated and/or completed with soluble enzyme versions exerting identical specificities in plasma and competing vice versa</em> 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 O<i>A</i> hybrid alleles at the normal A<i>B</i>O 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<i> </i>GalNAc-glycosylations occurring after the formation of the zygote have to be elucidated.