The material in gamma globulin ("reactant") which reacts with rheumatoid sera in the F II precipitin and F II tanned sheep cell agglutination tests was concentrated by precipitation with sodium sulfate. The concentrated "reactant" appeared to consist of polydispersed molecular aggregates of gamma globulin with s20 constants as high as 40, as well as the previously described inhomogeneous aggregated material.

Aggregated gamma globulin precipitated readily with most rheumatoid sera regardless of the reaction volume, and in low concentration inhibited the F II tanned sheep cell agglutination reaction and sensitized tanned erythrocytes to the agglutinating action of a positive rheumatoid serum. On the other hand, non-aggregated gamma globulin (7S) did not precipitate with rheumatoid sera and in low concentration did not inhibit the F II tanned sheep cell agglutination reaction, or sensitize tanned erythrocytes.

Non-aggregated gamma globulin in large excess inhibited the precipitin reaction of aggregated gamma globulin with "rheumatoid factor," and accounted for the characteristic shape of the whole F II precipitin curves and the volume effect described by Vaughan (relation of increased precipitate yield relative to the reaction volume in whole F II precipitin studies).

In serological systems other than the F II tanned sheep cell and F II precipitin reactions, the sensitization involves an antigen-antibody combination; i.e., sheep erythrocyte plus hemolysin in the sensitized sheep cell test, and egg albumin plus anti egg albumin in the absorption experiments with specific precipitates. The aggregation of gamma globulin that was essential for sensitization in the F II tanned sheep cell and F II precipitin tests may have simulated the aggregation of antibody gamma globulin that occurs with antigen-antibody union.

The present information has been incorporated into a schematic hypothesis for the basis of the rheumatoid serological reactions.

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