How A and B antigens are built, why anti-A and anti-B are there from infancy, subgroups, the Bombay phenotype and how to resolve grouping discrepancies, with MCQs and the full ABO quiz.
- Genes: ABO on chromosome 9q34 encodes glycosyltransferases; FUT1 (chromosome 19) makes the H antigen they build on
- Antibodies: naturally occurring IgM anti-A and anti-B appear at 3–6 months; they fix complement and cause intravascular haemolysis
- Subgroups: A2 makes up about 20% of group A; Dolichos biflorus lectin reacts with A1 only
- Bombay (Oh): no H antigen, potent anti-H; transfuse only Bombay blood
- Universal: O red cells and AB plasma
How ABO antigens are built
All ABO antigens start from the H antigen, made when the FUT1 fucosyltransferase adds fucose to a precursor chain. The ABO gene then decides what is added on top: the A transferase adds N-acetylgalactosamine, the B transferase adds D-galactose, and the O allele makes an inactive enzyme, leaving H unchanged. A separate gene, FUT2 (secretor), controls whether A, B and H substances appear in saliva and other secretions.
| Group | Red cell antigen | Plasma antibodies | Can receive red cells from |
|---|---|---|---|
| O | None (most H) | Anti-A, anti-B, anti-A,B | O only |
| A | A | Anti-B | A, O |
| B | B | Anti-A | B, O |
| AB | A and B | None | AB, A, B, O |
The amount of H antigen falls as more is converted to A or B: O > A2 > B > A2B > A1 > A1B. That is why Ulex europaeus (anti-H) lectin reacts most strongly with group O cells.
ABO antibodies
Anti-A and anti-B form without red cell exposure, probably after contact with similar carbohydrates on gut bacteria. They appear at about 3–6 months of age, so reverse grouping is not done in newborns. They are mainly IgM (group O people also make IgG anti-A,B), react at room temperature and body temperature, and activate complement. That is why an ABO-incompatible transfusion causes acute intravascular haemolysis.
A subgroups and the Bombay phenotype
| Phenotype | Key features | Clinical point |
|---|---|---|
| A1 | About 80% of group A; reacts with anti-A1 lectin (Dolichos biflorus) | — |
| A2 | About 20% of group A; fewer A sites, no reaction with anti-A1 lectin | Some A2 and many A2B people make anti-A1, usually cold-reacting and clinically insignificant |
| Weak A (A3, Ax, Am, Ael) | Mixed-field or very weak reactions | Cause forward–reverse discrepancies |
| Bombay (Oh) | No H on red cells (hh, and non-secretor); anti-A, anti-B and strong anti-H | Groups as O but reacts with all O cells; needs Bombay blood only |
Forward and reverse grouping
Forward (cell) grouping tests the patient’s red cells with anti-A and anti-B reagents. Reverse (serum) grouping tests the plasma against known A1 and B cells. The two must agree before a group is issued.
Grouping discrepancies
| Problem | Cause | Example |
|---|---|---|
| Missing or weak antibodies | Too young, elderly, hypogammaglobulinaemia, stem cell transplant | Reverse group weaker than expected |
| Missing or weak antigens | Weak A or B subgroups; leukaemia | Weak forward reaction |
| Extra antigens | Acquired B (bacterial deacetylation of A, in colorectal cancer or gram-negative sepsis); B(A) phenotype | Group A patient reacts with anti-B |
| Extra antibodies | Anti-A1 in A2 or A2B; cold alloantibodies or autoantibodies | Unexpected reverse reaction |
| Plasma protein problems | Rouleaux from myeloma or high-molecular-weight dextran | False agglutination in reverse grouping; saline replacement resolves it |
Pathology MCQPractice questions
Three quick questions, then the full quiz.
A patient groups as O on forward grouping, but her plasma agglutinates all group O screening cells, including her own group O donors. What is the most likely explanation?
Show answer
Which lectin is used to distinguish A1 from A2 red cells?
Show answer
A group A patient with colorectal carcinoma and E. coli sepsis now shows a weak reaction with anti-B. What is this?
Show answer
- A and B antigens are built on the H antigen; O has the most H.
- Anti-A and anti-B are naturally occurring IgM from 3–6 months of age.
- A2 is about 20% of group A; anti-A1 lectin separates A1 from A2.
- Bombay individuals make anti-H and need Bombay blood.
- Resolve forward–reverse discrepancies before issuing a group.
Cohn CS, Delaney M, Johnson ST, Katz LM, eds. AABB Technical Manual, 20th ed. AABB; 2020 · Harmening DM. Modern Blood Banking and Transfusion Practices, 7th ed. F.A. Davis; 2019 · Daniels G. Human Blood Groups, 3rd ed. Wiley-Blackwell; 2013
High-Yield, Board-Style Image MCQs & Interactive Whole Slide Images
High-resolution virtual microscopy with questions aligned to ABP, FRCPath, NEET-SS, DM Hematopathology and MD/DNB.
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