Why Do We Have Blood Types? A, B, O and the Rhesus Factor Explained

Red blood cells carry various molecules on their outer membrane, and the ABO system concerns one family of them: short chains of sugar. Everyone makes a base chain, called H. People of type A have an enzyme that adds one particular sugar to the end of it; people of type B have a slightly different enzyme that adds a different sugar; people of type AB have both enzymes and make both; people of type O have neither working enzyme and their cells carry the bare H chain. The letters are labels for which decoration the cells wear.

The genetics is simple enough to be a standard school example. A single gene has three common versions, A, B and O, and everyone carries two copies. A and B are dominant over O, so a person with one A and one O copy is type A, and only two O copies give type O. Two type A parents can therefore have a type O child, which has caused arguments in more than one family.

The reason blood type matters is not the sugar but the immune response to it. From the first months of life, people make antibodies against whichever ABO sugars their own cells lack, apparently because gut bacteria carry similar sugars and the immune system learns to attack the unfamiliar ones. A type A person has antibodies against B; a type B person against A; a type O person against both; a type AB person against neither.

Give a type A patient type B blood and their antibodies bind the transfused cells, which clump and burst, releasing haemoglobin into the bloodstream, clogging the kidneys and setting off a cascade of clotting and shock. It can kill within the hour. That is why type O red cells, which carry no A or B sugar for anyone's antibodies to attack, can be given to anyone in an emergency, and why type AB people, who have no such antibodies, can receive any type. The compatibility rules for red cells:

• •Type O: can donate to anyone, can receive only O
• •Type A: can donate to A and AB, can receive A and O
• •Type B: can donate to B and AB, can receive B and O
• •Type AB: can donate only to AB, can receive from anyone

The plus or minus after the letter is a separate system. The Rhesus factor, named after the monkeys it was first found in, is a protein on the red cell surface that about 85 percent of Europeans have and 15 percent lack; the proportions differ elsewhere, with almost all East Asians being positive. Unlike the ABO antibodies, antibodies against the Rhesus protein are not made in advance. A negative person makes them only after being exposed to positive blood, which means a first mismatched transfusion may pass but a second will not.

The exposure that matters most is pregnancy. A Rhesus-negative mother carrying a positive baby can be sensitised by the baby's blood at birth, and in a later pregnancy her antibodies can cross the placenta and destroy the next positive baby's red cells, a condition that killed thousands of newborns a year until the 1960s. It is now prevented by giving negative mothers an injection of ready-made anti-Rhesus antibody around the time of birth, which mops up any fetal cells before her own immune system notices them. There are dozens of other blood group systems beyond ABO and Rhesus, but these two account for nearly all transfusion reactions.

The ABO gene is at least twenty million years old and is shared with other apes, and the fact that the different versions have persisted for so long suggests they are being kept by natural selection rather than drifting. The likeliest explanation is disease. Pathogens use cell-surface sugars as handholds, and different types are vulnerable to different ones. Type O people are less likely to die of severe malaria, which may be why O is so common in the tropics, and more susceptible to cholera and to the stomach ulcer bacterium. Type A carries a higher risk of some cancers and of severe illness from certain viruses.

A population in which several types coexist is harder for any single pathogen to sweep through, which is the same logic that keeps many genes variable. The types are not better or worse. They are a hedge, distributed across the species, against whatever the next epidemic turns out to be. There is no good evidence that blood type affects personality, as a popular Japanese belief holds, or that eating for your blood type does anything.

The compatibility rules for red cells turn upside down when the transfusion is plasma, the liquid part of blood. Plasma carries the antibodies rather than the cells, so the question becomes which antibodies the donor's plasma contains. Type AB plasma has no anti-A or anti-B antibodies, so it can be given to patients of any ABO type, making AB people the universal plasma donors. Type O plasma contains both antibodies, so it can go only to type O patients. This is why blood services ask for different donations from different people, and why a person with a common type may be asked to give plasma instead of whole blood.

There are also rare types that break the simple picture. In 1952 doctors in Bombay, now Mumbai, identified people whose cells lack even the H base chain that everyone else uses to build A and B. Because they cannot make H, their blood looks like type O in a basic test, but their immune system makes antibodies against H, which every ordinary type O donor carries. They can safely receive blood only from someone with the same rare pattern. Cases like this are why hospitals cross-match donor and patient blood directly, rather than relying on the letter on a card alone.

A blood type is usually fixed for life, but in one routine situation it changes completely. Red blood cells are made in the bone marrow, so a patient who receives a stem cell or bone marrow transplant, often for leukaemia, starts producing the donor's red cells instead of their own. Donors are matched on tissue types that matter far more for the transplant's success, not on ABO group, so many recipients receive marrow of a different blood type. Over the following weeks and months their old red cells die off and are replaced, and a patient who was type A may become type O for good.

Scientists are also trying to change the type of donated blood on purpose. Since the A and B markers are sugars added to the H chain, an enzyme that snips off the extra sugar would make A or B cells behave like type O cells, usable for anyone. Researchers in the 1980s used an enzyme from green coffee beans to convert type B cells this way, but it worked too slowly. In 2019 a team in Canada reported far more efficient enzymes taken from bacteria in the human gut, which strip the A sugar quickly. The approach is promising but not yet in routine hospital use.

Humans are not the only animals with blood groups. Cats have a system with types A, B and the rare AB, and the antibodies they naturally carry make mismatched transfusions especially dangerous: a type B cat given type A blood can suffer a severe, sometimes fatal, reaction. Vets therefore test or cross-match cats before any transfusion.

The same danger affects kittens: a type B mother passes antibodies against type A in her milk, which can destroy a type A kitten's red cells, so breeders of some pedigree breeds test their cats before mating. Dogs have more than a dozen blood group systems, but their first transfusion is usually safer because they rarely carry natural antibodies against other types, though later transfusions require more care.

Blood types are defined by sugars and proteins on the surface of red cells and by the antibodies people carry against the ones they lack, which is why a mismatched transfusion destroys the donated cells. The ABO system depends on which sugar an inherited enzyme adds, the Rhesus factor is a separate protein that matters most in pregnancy, and the variety persists because different types resist different diseases.