HIGH MOLECULAR WEIGHT ANTIBODIES

Despite the fact that the existence of high molecular weight antibodies has been known for a long time, only recently have they received attention commensurate with their significance. Several explanations may be cited for this fact. First and perhaps foremost are the fallacious concepts that these antibodies occur in only a few species (particularly the horse) and that the rabbit and the human produce only low molecular weight antibodies in response to antigenic stimulus. This was based on early work with antipneumococcal antibodies, in which few animals were examined. It now appears that not only do many horses make low molecular weight antibodies but that rabbits can make the high molecular weight type, even to pneumococci.’ Of essential importance are the stage of immunization and variations among individual animals. Another factor hindering their recognition was the belief that high molecular weight antibodies were artifacts produced by the aggregation of y globulin under chemical treatment. The failure of Cann2 to find this species in human y globulin isolated by electrophoresis convection contributed significantly to this concept. I t is now clear that y globulin isolated by other methods of electrophoresis does contain a high molecular weight component, representing as much as 10 per cent of the total y globulin! The high molecular weight material is a clearly definable entity in human and rabbit serum, with physical and chemical properties totally different from ordinary7 globulin. Antibodies belonging to this class also show these very different properties. It is no longer possible to say that a given material is or is not an antibody on the basis of its properties; the class of antibody, whether the ordinary 7s antibody or high molecular weight type, must be considered. In addition to these, a third group of “immunoglobulins,” recently defined by Heremans, contains antibodies of still different properties, the &A proteins! There undoubtedly are further subgroups. Before discussing the various special characteristics of the high molecular weight immunoglobulins, it might be well to consider the various antibodies and other materials from human serum that have been classified in this fraction. A summary of the types of antibodies and antibodylike substances of human serum that have been found to belong, at least in part, to the high molecular weight class is given in TABLE 1. Of course, the prototype of these proteins is the Waldenstrom macroglobulins. Some of these appear to have specific antibodylike activity. Cold agglutinin activity6 and complement fixation activity with human cellular antigensa have been described. In addition, we have recently encountered two cases of typical Waldenstrom macroglobulinemia in which the pathological proteins had rheumatoid factor activity. One of these7 precipitates at very high dilutions with aggregated y globulin. It also gives some of the other rheumatoid factor reactions, such as those of the =-sensitized human cell and the Fr. I1 chromium-treated red cell. I t does