The human natural anti-A isoagglutinin dissolves from trans-species, germline Tn antigen
What is it about?
The human natural anti-A isoagglutinin, which arises most pronouncedly in blood group O(H) individuals, seems identical to the germline-encoded anti-A/Tn cross-reactive non-immune IgM molecule and might represent the authentic complementary protein to the native Tn carbohydrate structure, which occurs during every normal growth in volatile expressions. Innate antibodies remain involved in controlling the growth processes, from which they arise, and the Tn (serologically A-like) epitope and its complementary non-immune anti-A/Tn cross-reactive IgM most likely act, via a reversible oxygen bridge, as a functional unity in growth regulation. This principle may be clarified by lower metazoans, such as Helix pomatia, whose anti-A/Tn agglutinin has emerged from the coat proteins of fertilized eggs, while reflecting the snail-intrinsic reversible O-GalNAc glycosylations; the hexameric structure of this primitive invertebrate defense protein gives rise to speculation regarding an evolutionary relationship to the mammalian nonimmune, anti-A-reactive immunoglobulin M (IgM) molecule. In fact, the female C57BL/10 mouse demonstrates the developmental connection of reproduction and primitive immunological defense, in which similarly to Helix pomatia agglutinin, the anti-A/Tn cross-reactive, non-immune protein or ancestral immunoglobulin M is complementary to O-GalNAc-carrying ovarian glycolipids and is released into the plasma after completion of germ cell maturation. Finally, this murine anti-A antibody demonstrates identical serological reaction patterns to human innate anti‐A isoagglutinin.
Why is it important?
The evolution of the human ABO(H) blood group system clearly discriminates against the non-O blood groups A and B, with regard to immunity via impairment of the non-immune IgM polyreactivity due to A and B phenotypic, glycosidic accommodation, while in addition, these groups are excluded from the adaptive production of immunoglobulins against prokaryotic A/B cross-reactive antigenic structures due to clonal selection. Malignant growth does not occur in lower metazoans, such as snails, but in higher organisms appears to be favored by the more complex metabolic pathways and higher number of mutations, associated with the progress of species and phenotype diversity.
The following have contributed to this page: Peter Arend