ABO Blood Type Discovery

Karl Landsteiner discovered the two most significant blood type systems during early experiments with blood transfusion: the ABO group in 1901 and in co-operation with Alexander S. Wiener, the Rhesus group in 1937.

Development of the Coombs test in 1945, the advent of transfusion medicine, and the understanding of ABO hemolytic disease of the newborn led to discovery of more blood types. The International Society of Blood Transfusion (ISBT) now recognizes 30 human blood type systems. Across the 30 blood types, more than 600 different blood type antigens have been identified; many are very rare or are mainly found in certain ethnic groups.

Blood types have been used in forensic science and were formerly used to demonstrate impossibility of paternity (e.g., a type AB man cannot be the father of a type O infant), but both of these uses are being replaced by genetic fingerprinting, which provides greater certainty.

What Determines Blood Type?

ABO blood types are determined by a cell surface marker that identifies the cell as belonging to “self” or to that individual. These cell surface markers are characterized by a protein or lipid that has an extension of a particular arrangement of sugars. Figure below shows the arrangement of sugars that determines each of the A, B, and O blood types. Note that each is identical, except that types A and B have an additional sugar: N-acetylgalactosamine for A, and galactose for B.

Figure 1: ABO blood group system

Diagram showing the carbohydrate chains that determine the ABO blood group

ABO-antigen

These sugar arrangements are part of an antigen capable of stimulating an immune response that produces antibodies to identify and destroy foreign antigens. People with blood type A produce antibody B when exposed to antigen B, and those with blood type B produce antibody A when exposed to antigen A. Blood type AB, however, produces no antibodies because both antigens present on the cells are recognized as “self.” Blood type O produces antibodies A and B, because neither antigen A nor B is present on the cells of type O individuals. Antibodies A and B belong to the “M” class of immunoglobins and are expressed from the immunoglobin genes of B-cell lymphocytes upon exposure to foreign antigens. Immunoglobin genes are capable of producing an essentially infinite number of antibodies through a complex editing and selective process. Consequently, there isn’t a specific “antibody A” gene or “antibody B” gene inherited with a complementary A or B antigen.

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A gene for the specification of antigens A or B or type O determines the blood type. An enzyme, glycosyltransferase, is the product of this gene, and differences in the sequence of this enzyme (polymorphisms) determine whether the enzyme attaches N-acetylgalactosamine (antigen A), galactose (antigen B), or no sugar (type O) see Figure 1. People inherit two genes for blood type; or, more accurately, two alleles, one from each parent. These alleles are represented as IA for type A, IB for type B, and i for type O. Both glycosyltransferase alleles for antigens A and B are expressed when inherited together, producing both antigens and resulting in blood type AB. When the allele for blood type A or B is inherited withtype O, the individual will be either type A or B. This is not necessarily because the type O allele is silenced or recessive, but is instead a result of the activity of the A or B glycosyltransferase, while the glycosyltransferase for the O allele is inactive. A type O individual has both alleles for the inactive glycosyltransferase.