Variable region domain exchange influences the functional properties of IgG.

In the present study we have characterized a family of anti-dansyl Abs with the variable region of the heavy chain on human Ckappa and the variable region of the light chain on different human gamma constant regions (creating inside-out molecules). Although fully assembled molecules were secreted, this variable region exchange slowed the kinetics of Ab assembly. Although the variable region exchange does not lead to a detectable change in the microenvironment of the combining site, it did alter the kinetic parameters of binding to immobilized Ag, slowing both the on and off rates. When effector functions were evaluated, inside-out IgG1 and IgG3 were more effective in complement-mediated cytolysis than their wild-type counterparts. Variable region domain exchange may be one approach to obtaining Abs of identical specificity with altered binding characteristics.