ABO phenotype-protected reproduction based on human specific α1,2 L-fucosylation as explained by the Bombay type...

The metabolic relationship between the formation of the ABO(H) blood group phenotype and human fertility is evident in the case of the (Oh) or Bombay blood type, which Charles Darwin would have interpreted as resulting from reduced male fertility in consanguinities, based on the history of his own family, the Darwin/Wedgwood Dynasty. The classic Bombay type occurs with the extremely rare, human-specific genotype (h/h; se/se), which (due to point mutations) does not encode fucosyltransferases 1(FUT1) and 2 (FUT2). These enzymes are the basis for ABO(H) phenotype formation on the cell surfaces and fucosylation of plasma proteins, involving neonatal immunoglobulin M (IgM). In the normal human blood group O(H), which is not protected by clonal selection with regard to environmental A/B immunization, the plasma contains a mixture of non-immune and adaptive anti-A/B reactive isoagglutinins, which in the O(h) Bombay type show extremely elevated levels, associated with decreased levels of fucosylation-dependent functional plasma proteins, suchs as the van Willebrand factor (vWF) and clotting factor VIII. In fact, while the involvement of adaptive immunoglobulins remains unknown, poor fucosylation may explain the polyreactivity in the Bombay type plasma, which exhibits pronounced complement-binding cross-reactive anti-A/Tn and anti-B IgM levels, with additional anti-H reactivity, acting over a wide range of temperatures, with an amplitude at 37 °C. This aggressive anti-glycan-reactive IgM molecule suggests the induction of ADCC (antibody-dependent) and/or complement-mediated cytotoxicity via overexpressed glycosidic bond sites against the embryogenic stem cell-to-germ cell transformation, which is characterized by fleeting appearances of A-like, developmental trans-species GalNAcα1-O-Ser/Thr-R glycan, also referred to as the Tn (T "nouvelle") antigen.