The Role of Negative Charge in the Complement-Dependent Dissoeiation of IgG-Mediated Aggregation

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Abstract
The IgG-mediated aggregation of yeast particles was used as a model to study the dissociating effect of human serum complement on immune aggregates. A 92% decrease in non-aggregated particles was obtained by coating particles with IgG. After incubation of the aggregates in normal human serum (NHS) at 37.degree. C the number of free particles increased .apprx.10 times. The effect could be obtained with ethyleneglycol-bis(b-aminoethyl ether)-N,N''-tetraacetic acid-containing serum but not EDTA containing serum, indicating the importance of the alternate pathway of complement activation. Treatment with NHS did not release anti-yeast IgG from the particles, indicating that disruption of antigen-antibody bonds did not explain the phenomenon. The negative charge of the different particles was studied by measuring the interaction to diethylaminoethyl-Sephacel beads. Compared with non-coated and IgG-coated particles, the NHS-treated particles were not released until the ionic strength increased to 200 mM NaCl or the pH decreased to 4.4., indicating a strong negative charge of NHS-treated particles. It is proposed that complement increases the negative charge of immune complexes, thereby inducing repulsive forces that counteract Fc-Fc interactions and increase the solubility of the complexes.