Properties and modifications of a cryomacroglobulin possessing cold agglutinin activity

The physical properties of a pathological γ M ‐globulin with cold agglutinin activity and cryoglobulin solubility could be modified by changes in temperature and pH and upon dilution. The type of changes noted appear to simulate those expected in a readily dissociable antigen‐antibody complex. Naturally occurring and chemically produced subunits of the γ M ‐globulin and Fc‐fragments of myeloma proteins diminished the cryoproperty of the γ M ‐globulin and effected changes in its physical properties but did not alter its cold agglutinin activity. Cryoglobulin properties could be conferred upon some purified γ M ‐globulins by reacting them with Fc‐fragments. Mercaptan dissociation of the Cryomacroglobulin produces subunits with loss of the noted activities. Reaggregation of these subunits restores some of the native properties, but variable results which are dependent on the type of mercaptan employed are obtained. Attempts to explain the cold agglutinin activity of γ M ‐globulin hybrids containing variable amounts of mercaptan‐produced active and inert subunits suggest that activity requires two of the five subunits to be derived from the γ M ‐cold agglutinin and to be adjacent to each other.