Introduction

Abstract

For IgM a strictly associative model cannot be correct since it appears that a single molecule of IgM acquires the ability to bind and activate C1 when the IgM becomes attached to a cell surface. Indeed, IgM has the advantage of being a “built-in” aggregate, so that the degree of intermolecular crosslinking is not a variable altered by attachment. Since IgM is already an aggregated structure, this implies that sites on the Fc responsible for the activation of complement cannot be exposed or preformed to a significant extent prior to the interaction of the combining sites on the Fab with antigen; thus a conformational change in the structure of the Fc region seems essential. However, there does appear to be some interaction between unliganded IgM in solution and C1q. If we accept the concept that the structure of a protein in solution is not static but rather a dynamic equilibrium between all of its kinetically accessible forms, then the sites which interact with complement may flicker into and out of existence prior to the interaction of IgM with antigen. In this case, there would be a small background rate of complement binding and, perhaps, activation in solutions of unaggregated and unliganded IgM. Then, when IgM binds to a cell surface, this dynamic equilibrium would be much shifted in favor of the forms possessing the sites which interact with complement, and in consequence the rate would be greatly enhanced. This shift in the dynamic equilibrium of protein structures would then represent the conformational change.