The ABO blood type divides each blood type according to whether they have the "A" and "B" antigen(s) (AB has both, O has none). People also have antibodies against the antigens they don't have (AB has none, O has both), even before they have ever come in contact with those antigens.

Why do people have antibodies against these antigens they have never come in contact with? This isn't the normal situation for the immune system (e.g. for a virus or the blood type rhesus factor)

  • 2
    $\begingroup$ The only reasonably satisfying exploitation I've ever heard is that human gut flora contains the A and B antigens and thus antibodies are created in a reaction to that. But I've never found satisfying reference material or sources for that explanation. $\endgroup$
    – dtech
    Jan 9, 2013 at 2:00
  • $\begingroup$ I am not sure I understand your question fully. The specific immune system has the potential to make antibodies for lots and lots and lots of antigens it has never come in contact with. Essentially every time you get a cold it is the specific immune system producing antibodies for an antigen that it had not encountered. If it had encountered it before, then you would have memory cells and likely wouldn't get sick. In reality it is amazing that we have so few blood antigens and that we can transfer blood as easily as we do. $\endgroup$
    – DQdlM
    Jan 9, 2013 at 18:01
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    $\begingroup$ @DQdlM The difference is: normally you will not have antibodies for antigens you have not come in contact with. E.g. when first encountering a specific type of influenza you will start making antibodies against it. This is why vaccination works. But blood antibodies are special: you already have antibodies for blood antigens even if you've never come into contact with other blood. $\endgroup$
    – dtech
    Jan 9, 2013 at 22:19
  • $\begingroup$ interesting. So the antibodies are present in the blood even w/o exposure to the antigen? I always assumed that we just had the potential to make the antibodies if the antigen was encountered. I will have to look into this a little more. $\endgroup$
    – DQdlM
    Jan 10, 2013 at 1:11
  • 1
    $\begingroup$ It is written in "Biology - Campbell and Reece " that development of the antibodies occur due to microbes living in our body having antigens similar to other blood group's antigens. $\endgroup$
    – biogirl
    Jun 8, 2013 at 11:31

3 Answers 3


According to the Wikipedia entry for the ABO blood group system:

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 cited reference is Van Oss, CJ (2004) Letter to the Editor: "Natural versus Regular Antibodies The Protein Journal 23:357, available here. This source contains this statement:

..."we have known for more than four decades that these bloodgroup (antibodies) arise out of minor infections occurring very early in life..."

The cited references are:

Pettenkofer et al. Z. ImmunForsch. 119: 415-429

Springer, GF (1960) Klin. Wschr. 38: 513-514

Unfortunately I have access to neither of these articles, and besides they are presumably written in German.


We each inherit either A, B, AB or no antigens from our parents.

The current thought is that when you're between 0-6 months old you are exposed to bacteria/viruses that contain very similar antigens (A or B). These antigens are similar enough to the A and B antigens found on red blood cells that any antibody created against these bacterial antigens would also react against the corresponding red blood cell antigen. Seeing as you can't produce an antibody against your own antigen (except in rare circumstances), you always produce the opposite antibody to what antigen you have.

I hope some of that makes sense. Feel free to point out any glaring mistakes I've made, wouldn't be the first time! ;-)

Source: I'm a biomedical scientist.


I am posting so long after the initial question as I replied to a more recent similar question that was marked as a duplicate. On being redirected here I was surprised at the answers as the question (and certainly that of the supposed duplicate) did not give any indication that he was aware that the situation for non-compatible blood-group antigens was any different from any other foreign antigens. I think it appropriate, therefore, to append the following (@KennyPeanuts has also commented in this vein) for the benefit of those unfamiliar with the idea of clonal selection.

To put it simply, clonal theory of antibody selection assumes that the antigen-specificity of antibody-producing cells is random, so that all types of specificity will exist. On encountering an antigen a particular cell will be stimulated to divide and hence allow the production of a greater amount of antibody against the antigen.

Immune tolerance requires that cells producing antibody against self antigens be eliminated at some stage. Hence people of blood group O, lacking blood-group antigens A and B, will not have become tolerant to them, and will have antibody-producing cells capable of producing antibodies against them, should they encounter them in an incorrect blood transfusion.

  • $\begingroup$ I think your answer does not invalidate the others, but it is a requirement? The existence of A/B antigen specific naive B cells is necessary, but those B cells will not produce antibodies until exposed to the antigens (in the context of an inflammatory response). The above answers argue that the "exposure" comes from infection with pathogens that have antigens similar enough to the A/B antigens as to cause cross-reactivity. So the activated B cells will produce antibodies against the pathogen antigens that also recognize A and/or B antigens in blood cells. $\endgroup$
    – ddiez
    Jul 11, 2016 at 5:32
  • $\begingroup$ @ddiez — OK. I've modified my answer taking your remarks into account. I still suspect that one of the questioners (the one who posted the supposed duplicate) had no knowledge of the special situation for blood group antigens (I certainly didn't) and that my answer forms a basic introduction which the other answers lack. $\endgroup$
    – David
    Jul 11, 2016 at 15:37

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