Reduction and alkylation of human gamma globulin prior to aggregation results in a loss of complement-fixing ability, and retention of the capacity to react with rheumatoid factor. The addition of aggregated, reduced gamma globulin to serum containing high titers of rheumatoid factor produces a typical bell-shaped precipitin curve with an equivalence point and little precipitate in the region of antigen excess. Since aggregated, reduced gamma globulin fixes little complement by itself, it was possible to determine whether its reaction with rheumatoid factor fixes com-NVESTIGATIONS of the structure of gamma I globulin have defined 2 distinct portions of the molecule: one that contains the antibody combining site, and the other responsible for a variety of biologic properties. These properties include the ability to fix to skin and give passive cutaneous anaphylaxis, the capacity to cross the placental membrane, reactivity with rheumatoid factors, and complement fixation.1 The struc-plement. Under appropriate conditions rheumatoid factor can fix complement. When aggregated, reduced gamma glo- bulin was added to heat-inactivated sera with varying titers of rheumatoid f a e tor, no fixation of guinea pig or human complement was observed. But pre- formed complexes of rheumatoid factor and gamma globulin will fix human complement at 37 C. Intradermal injection of 40 pg N of aggregated, r e d u d gamma globulin into control subjects or patients with rheumatoid arthritis produced no immediate or delayed skin reactions.
tures essential for the induction of biologic activities also appear to be dependent on disulfide linkages, since treatment with sulfhydryl reducing agents followed by alkylation results in a loss of many of these properties. Wiedermann, Miescher and Franklin observed that when 7s human antibodies or heat-aggregated human gamma globulin were reduced with 2-mercaptoethanol, they lost the ability to fix com-Supported in part (N.J.Z.