Fourteen commercial pooled human γ-globulin (HGG) preparations varied widely in their ability: a) to sensitize tanned sheep red cells for agglutination with rheumatoid arthritis serum (RAS), b) to precipitate with RAS, and c) to inhibit agglutination of sensitized tanned sheep red cells by RAS. The inhibitory power of any given γ-globulin preparation paralleled its sensitizing and precipitating capacity. There was little correlation between these reactions and the amount of aggregates present in the γ-globulin preparations.
Different preparations of aggregated HGG also varied in their inhibitory power and precipitating capacity but, when the aggregates were heated, their reactivity increased to about the same level in all cases.
The inhibitory power of purified aggregated HGG was found to increase with the heating time employed in their preparation. When the aggregates were dissolved in alkali, this effect was abolished and reactivity decreased to a uniform level.
Purified 7 S HGG, when denatured under conditions that avoided aggregation, was also found to be reactive with RAS.
From these results it has been concluded that reactivity of pooled HGG for serum rheumatoid factors is primarily due to denaturation. Subsequent aggregation of the denatured globulin enhances its reactivity, probably because of decreased solubility of the rheumatoid factor-γ-globulin complex.