Development of anti-D may occur when Rh-negative individuals are exposed to D-positive red cells; however, the development of anti-D varies greatly from person to person.
- Some Rh-negative individuals produce anti-D after being exposed to a small volume of D-positive red cells (e.g., 0.1 mL).
- Some Rh-negative individuals must be exposed to a relatively large volume of D-positive cells to produce anti-D.
- Some Rh-negative individuals will never produce anti-D, regardless of exposure.
Because about 30% of Rh-negative people seem incapable of producing anti-D, no matter how many exposures to the D antigen, it was once thought that anti-D production was partially controlled by major histocompatibility complex immune response genes. Later studies have not confirmed the association.
