Central immunological position of the human histo (blood) group O(H)
Prokaryotic "blood group A/B-like" antigenic structures apparently induce basically cross-reactive anti-A/B immunoglobulins, which due to clonal selection neither arise in blood group A nor in B individuals but occur exclusively in blood group O. While bacterial endotoxins non-specifically stimulate the formation of all immunoglobulins, most likely involving the anti-A/B isoagglutinins, a definite, adaptive immunological induction of these agglutinins appears to be restricted to blood group
... to blood group O(H) individuals. In the non-O blood groups, anti-A/B reactivity is exerted by a primarily blood group-independent, polyreactive and thymus-independent non-immune IgM molecule that has undergone the phenotype-specific, glycosidic accommodation of plasma proteins, which reduces or excludes anti-self reactivity, however, necessarily involves impairment of immunity. While blood group A phenotype development thus is associated with impairment of both adaptive and innate immunity, it promotes susceptibility to malaria infection via these intrinsic enzyme functions, initiating a self-destructive glycosidic, phenotypic accommodation of a "wrong eukaryote". In fact, blood group A phenotype-specific GalNAc transferase(s), expressed by both cell surfaces and plasma proteins, and serine/threonine kinases, which are imported from Plasmodium falciparum into the red cell membrane, might provide the metabolic condition for adhesion protein and rosette formation, assumingly based on heterologous O-glycosylation, breaking a species barrier and completing the "serine repeat antigen". This potentially requires a new molecular definition of the therapeutic target, and the lack of blood group A/B-specific phenotype glycosylations might explain the superior adaptive and innate immunity of the human blood group O(H) and its obvious protection from severe malaria infection, which currently is discussed to contribute to the global distribution of ABO blood groups in the human population.