The presence of cryoprecipitable immunoglobulins in normal human sera may reflect specific molecular interactions.

The nature of the minute amounts of cryoprecipitable proteins present in all normal sera has been investigated in particular relation to the physicochemical and functional properties of the precipitated immunoglobulins. Cryoprecipitated material from 48 normal donor sera were first analyzed for their protein, IgG and IgM content. SDS-PAGE analysis revealed many bands in a majority of samples but in about one third a very limited number of bands was observed. IgM, IgG and albumin were identified and a lower molecular weight component (16 KD) was always present. Restricted clonality was demonstrated by IEF in 25-30% of the samples. In 50% of cryoprecipitates IgG was present in higher molecular weight fractions than 7S on sucrose density gradient at neutral pH. Ultracentrifugation at acid pH lead to a dissociation of these IgG fractions in most of the samples. A positive reaction for IgM rheumatoid factor was seen in 63% of the samples and there was a specific enrichment of RF activity in cryoprecipitates as compared to the corresponding serum. These data suggest that the cryoprecipitation of immunoglobulins in normal serum reflects specific interactions between immunoglobulin molecules rather than merely a non-specific precipitation of cold-insoluble molecules.