Histo (blood) group O “inbreeding” as it relates to A-allelic functions and ancestral IgM formation; a hypothesis *

Abstract

The development of human ABO blood group phenotypes and isoagglutinin specificities are thought to be associated with the release of the ancestral IgM molecule in an enzymatic process that is initiated by germ cell maturation, exposing the genetic history of organisms in haploidizations. The synthesis of O-GalNAc-linkages represents the first step of protein glycosylations in vertebrate ontogeny, and it is hypothesized that embryonic stem cell (ESC) germ cell transformation occurs under transient, non-somatic “A-like” O-GalNAc glycosylation in any species and phenotype of the ABO family, while over the course of maturation ancestral glycans undergo deglycosylations. Consequently, glycan-depleted complementary (glyco) proteins should become released from cell-adhesion molecules (CAMs) into the circulation, where “lost” ancestral specificities are mirrored in complementary glycosidic sites at the circulating IgM variable domains. Moreover, when humoral and cell-mediated immunity are decribed to get enhanced by gonadectomies, the nonsomatic origin of the innate anti-A reactive IgM, occurring in the C57BL/10 mouse, becomes unmasked by an ovariectomy performed before the onset of puberty. In fact, this anti-A being complementary with syngeneic ovarian glycolipids, appears strongly retarded, or does not appear at all in ovariectomized animals and likely emerges from GalNActransferase depletion having completed oocyte maturation instead. The early IgM molecule, thus arising hypothetically in developmental non-somatic cell divisions or fusions, highly suggests substrate competition with subsequent O-glycosylations in ongoing ESC germ cell transformations, while somatic GalNAc transferases in the human blood group A, coming into force after generation of the zygote, are competing vice versa by glycosylation of cell adhesion proteins and hydrophilic glycolipid residues. This means competition by blood group A phenotype formation or “clearance of antibody by glycosylation”