The difference in the ability of IgG and IgM antibodies to agglutinate Rh+ (Rh-positive) red blood cells (RBCs) is primarily due to their structural and functional characteristics.
Size and valency: IgM antibodies are larger molecules with a pentameric structure, meaning they have ten antigen-binding sites (valency of 10). This enables IgM antibodies to cross-link multiple antigens on the surface of RBCs simultaneously, leading to efficient agglutination. In contrast, IgG antibodies are smaller and have a monomeric structure with only two antigen-binding sites (valency of 2), which limits their ability to form strong cross-links between RBC antigens.
Avidity: IgM antibodies have higher avidity, which refers to the overall strength of antigen-antibody interactions. Their multiple binding sites enable them to bind more strongly to the antigen on RBCs, enhancing the agglutination process. IgG antibodies, with fewer binding sites, generally have lower avidity and are less efficient at agglutination.
Affinity maturation: IgG antibodies are produced at a later stage during the immune response and undergo affinity maturation, a process that fine-tunes the binding specificity and strength of the antibodies to their target antigens. This maturation process results in increased affinity for the specific antigen but usually does not lead to an increase in valency. Consequently, although IgG antibodies become more specific for the Rh antigen, they still lack the valency advantage of IgM antibodies.
Activation of complement system: IgM antibodies have the unique ability to activate the complement system effectively. When complement proteins are activated, they can form large protein complexes that cause RBC lysis and further promote agglutination. IgG antibodies, in general, have a more limited capacity to activate the complement system and may not lead to the same degree of agglutination.
Due to these structural and functional differences, IgM anti-Rh antibodies are more efficient at causing agglutination of Rh+ RBCs, which can be of significant clinical concern in situations such as Rh incompatibility during pregnancy. This is why it's essential for medical professionals to closely monitor and manage Rh sensitization to prevent hemolytic disease of the newborn and other complications related to Rh incompatibility.