Antigenic stimuli: The antibodies in the ABO system are mainly naturally occurring, i.e., they are non-red cell stimulated. They can also be called regularly-occurring because if an antigen is missing, the corresponding antibody is always present.

Immunoglobulin class: Most people have anti-A and anti-B that is mainly IgM but also have a small amount of IgG anti-A and anti-B, and even traces of IgA. Some people have large amounts of immune (IgG) anti-A and anti-B. Immune anti-A and anti-B can be stimulated by exposure to A and B antigens on red cells, white cells or platelets, by injection of soluble A and B antigens (to boost titres prior to plasmapheresis for antisera), and by some vaccinations which contain bacterial A- and B-like antigens. Group O people in particular tend to make more IgG anti-A and anti-B than the other groups.

Variation with age: Anti-A and anti-B are not normally present at birth because newborns cannot synthesize immunoglobulins due to their underdeveloped immune system. If present at birth, anti-A and anti-B are IgG and of maternal origin. The antibodies develop between 3 - 6 months of age due to unknown antigenic stimuli, presumably bacteria and foodstuffs. They reach their highest level between 5 - 10 years of age, remain fairly constant in adulthood, and slowly decline in old age. In very old people, they can sometimes be very weak and may even appear to be missing in immediate spin tests done at RT. Often these weak ABO antibodies can be detected by doing the ABO grouping at low temperatures, e.g., 4°C.

Clinical significance: Anti-A and anti-B are clinically significant, because even though they react best at 4°C, they also can react at body temperature (37°C) and destroy red cells in vivo . Moreover, they are excellent complement binders and can bind C9 and cause IVH.

Phases of reactivity: Anti-A and anti-B usually react best in saline phases at 4°C. They can also react in saline phases at RT and 37°C, and in enzyme and antiglobulin phases.

IgG anti-A and anti-B: IgG anti-A and anti-B are unusual in two ways:

  1. Even though they are IgG, they can agglutinate red cells suspended in saline. This may be because of the large numbers of A and B antigens on red cells (1/4 to 1 million antigen sites per red cell).

  2. They can bind C9 and cause hemolysis (in vivo and in vitro ) even better than IgM anti-A and anti-B can. Normally IgM antibodies are better complement binders than IgG antibodies are because complement requires two Fc fragments close together in order to bind.

    Therefore, two IgG molecules are required for complement to bind, but only one IgM molecule (which is a pentamer with 5 Fc fragments) is required for complement to bind. Why IgG anti-A and anti-B can bind complement better than IgM anti-A and anti-B is unknown.

Enrichment Activity 2

Read ABO antibodies and age, a Medline abstract of a study investigating age-related changes in anti-A and anti-B titres.

Answer the following questions based on the abstract and e-mail replies to Pat.

  1. In investigating how ABO antibody strength relates to age, what did the researchers find affected strength more: age or individual variation?

  2. Which belief about ABO antibodies did the study confirm?

  3. Which belief did the study's data not confirm?

  4. The authors note that current beliefs about ABO antibodies and age are based on a study done in 1929. E-mail a comment or a question to the class mailing list about how this could happen, i.e., about how we can base today's so-called "facts" on only one study done so long ago.

  5. In your comment to the class list, suggest ways that can we determine which study is more correct, i.e., the 1929 or 1993 study?