ABO antigens
The H antigen is an essential precursor to the ABO blood group antigens. The H locus is located on chromosome 19. It contains 3 exons that span more than 5 kb of genomic DNA, and it encodes a fucosyltransferase that produces the H antigen on RBCs. The H antigen is a carbohydrate sequence with carbohydrates linked mainly to protein (with a minor fraction attached to ceramide moiety). It consists of a chain of β-D-galactose, β-D-N-acetylglucosamine, β-D-galactose, and 2-linked, α-L-fucose, the chain being attached to the protein or ceramide.
The ABO locus is located on chromosome 9. It contains 7 exons that span more than 18 kb of genomic DNA. Exon 7 is the largest and contains most of the coding sequence. The ABO locus has three main alleleic forms: A, B, and O. The A allele encodes a glycosyltransferase that bonds α-N-acetylgalactosamine to D-galactose end of H antigen, producing the A antigen. The B allele encodes a glycosyltransferase that joins α-D-galactose bonded to D-galactose end of H antigen, creating the B antigen.
In case of O allele, the exon 6 contains a deletion that results in a loss of enzymatic activity. The O allele differs from the A allele by deletion of only one nucleotide – guanine at position 261. The deletion causes a frameshift, and results in premature termination of translation, and thus, degradation of the mRNA. This results in H antigen remaining unchanged in case of O groups.
The majority of the ABO antigens are expressed on the ends of long polylactosamine chains attached mainly to band 3 protein, the anion exchange protein of the RBC membrane, and a minority of the epitopes are expressed on neutral glycosphingolipids.
Serology
Anti-A and anti-B antibodies (called isohaemagglutinins), which are not present in the newborn, appear in the first years of life. They are isoantibodies, that is, they are produced by an individual against antigens produced by members of the same species (isoantigens). Anti-A and anti-B antibodies are usually IgM type, which are not able to pass through the placenta to the fetal blood circulation. O-type individuals can produce IgG-type ABO antibodies.
Origin theories
It is possible that food and environmental antigens (bacterial, viral, or plant antigens) have epitopes similar enough to A and B glycoprotein antigens. The antibodies created against these environmental antigens in the first years of life can cross-react with ABO-incompatible red blood cells that it comes in contact with during blood transfusion later in life. Anti-A antibodies are hypothesized to originate from immune response towards influenza virus, whose epitopes are similar enough to the α-D-N-galactosamine on the A glycoprotein to be able to elicit a cross-reaction. Anti-B antibodies are hypothesized to originate from antibodies produced against Gram-negative bacteria, such as E. coli, cross-reacting with the α-D-galactose on the B glycoprotein.
The "Light in the Dark theory" (DelNagro, 1998) suggests that, when budding viruses acquire host cell membranes from one human patient (in particular, from the lung and mucosal epithelium where they are highly expressed), they also take along ABO blood antigens from those membranes, and may carry them into secondary recipients where these antigens can elicit a host immune response against these non-self foreign blood antigens. These viral-carried human blood antigens may be responsible for priming newborns into producing neutralizing antibodies against foreign blood antigens. Support for this theory has come to light in recent experiments with HIV. HIV can be neutralized in "in-vitro" experiments using antibodies against blood group antigens specifically expressed on the HIV-producing cell lines.
The "Light in the Dark theory" suggests a new novel evolutionary hypothesis: There is true communal immunity, which has developed to reduce the inter-transmissibility of viruses within a population. It suggests that individuals in a population supply and make a diversity of unique antigenic moieties so as to keep the population as a whole more resistant to infection. A system set up ideally to work with variable recessive alleles.
However, it is more likely that the force driving evolution of allele diversity is simply negative frequency-dependent selection; cells with rare variants of membrane antigens are more easily distinguished by the immune system from pathogens carrying antigens from other hosts. Thus, individuals possessing rare types are better equipped to detect pathogens. The high within-population diversity observed in human populations would, then, be a consequence of natural selection on individuals
Nonantigen biology
The carbohydrate molecules on the surfaces of red blood cells have roles in cell membrane integrity, cell adhesion, membrane transportation of molecules, and acting as receptors for extracellular ligands, and enzymes. ABO antigens are found having similar roles on epithelial cells as well as red blood cells.
Transfusion reactions
Due to the presence of isoantibodies against non-self blood group antigens, individuals of type A blood group immediately raise anti-B antibodies against B-blood group RBCs if transfused with blood from B group. The anti-B antibodies bind to B antigens on RBCs and cause complement-mediated lysis of the RBCs. The same happens for B and O groups (which raises both anti-A and anti-B antibodies). However, only blood group AB does not have anti-A and anti-B isoantibodies. This is because both A and B-antigens are present on the RBCs and are both self-antigens, hence they can receive blood from all groups and are universal recipient.
As far as transfusion compatibility is concerned, it is not strictly as simple as matching A, B, and O groups. In other words, no individual will ever receive a blood transfusion based on the ABO system alone. The rhesus factor must also be considered. Together, the rhesus factor and ABO grouping are the two most important compatibility factors to consider. An individual may be Rh+ or Rh-. In simpler terms, if an individual is blood type A and positive for the rhesus factor, then he or she is deemed "A+".
History of discoveries
The ABO blood group system is widely credited to have been discovered by the Austrian scientist Karl Landsteiner, who found three different blood types in 1900; he was awarded the Nobel Prize in Physiology or Medicine in 1930 for his work. Due to inadequate communication at the time it was subsequently found that Czech serologist Jan Janský had independently pioneered the classification of human blood into four groups, but Landsteiner's independent discovery had been accepted by the scientific world while Janský remained in relative obscurity. Janský's classification is however still used in Russia and states of former USSR (see below). In America, Moss published his own (very similar) work in 1910.
Landsteiner described A, B, and O; Alfred von Decastello and Adriano Sturli discovered the fourth type, AB, in 1902. Ludwik Hirszfeld and E. von Dungern discovered the heritability of ABO blood groups in 1910–11, with Felix Bernstein demonstrating the correct blood group inheritance pattern of multiple alleles at one locus in 1924. Watkins and Morgan, in England, discovered that the ABO epitopes were conferred by sugars, to be specific, N-acetylgalactosamine for the A-type and galactose for the B-type. After much published literature claiming that the ABH substances were all attached to glycosphingolipids, Laine's group (1988) found that the band 3 protein expressed a long polylactosamine chain that contains the major portion of the ABH substances attached. Later, Yamamoto's group showed the precise glycosyl transferase set that confers the A, B and O epitopes.
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