A central question of molecular immunology is “How does the binding of antigen to antibody induce the immune response?” In order to explore this question at the molecular level, three models have been devised1,2 for the generation of the immunologic signal between the Fab and Fc regions of antibodies: 1) the allosteric model; 2) the distortive model; and 3) the associative model. For IgG, using complement activation as a measure of immune response, most of the evidence indicates that association is a necessary step for signal generation. What is not clear, however, is whether association of IgG is the sufficient step for complement activation or whether a conformational change in IgG structure induced by antigen must also accompany the association. For IgM, on the other hand, a conformational change appears to be essential for complement activation, since a single molecule of IgM acquires the ability to bind and activate C1 when it becomes attached to a cell surface through two or more combining sites. IgM is already a pentameric molecule, and this “built-in” association also appears to be a necessary feature for efficient complement activation. Therefore, signal generation in IgM has been described as a mixture of models, associative, but also requiring a conformational change.