Polyreactive antibodies in multidonor-derived immunoglobulin G: Theory and conclusions drawn from experiments

Abstract

Multidonor-derived (md) preparations of IgG antibodies, agents of therapeutic potential, contain molecules interacting at clonal concentrations (concns) and with affinities recently estimated to cover a considerable range. Here we demonstrate that polyreactivity of the monomeric molecules represents the essential driving force of formation of the main reaction product, the IgG-dimers. This conclusion is obtained by applying the principles of the law of mass action to dimer formation by polyreactive monomeric reactants. In addition, general interrelationships involving the mean number of reactants per reactor, the experimental dimer portion (w/w) and the mean concentrations of monomers in a polyreactive and monoreactive antibody system are derived. These interrelationships, together with quantitative results obtained from simplified computational kinetic models of polyreactive antibodies, allow to estimate a remarkably high value for the mean number of reactants per reactor, exceeding 60 for the underlying IgG preparation obtained from pooled human plasma units of 5000 donors. Moreover, the potential origin and other consequences of polyreactivity are outlined.