Biosynthesis of low molecular weight (7S) and high molecular weight (19S) immunoglobulin M.

The class of immunoglobulin M (IgM) characterized by high molecular weight proteins with a sedimentation coefficient of 19S, includes a smaller molecular form with an S(20,[unk]) of approximately 7. The synthetic origin of the 7S IgM was investigated by biosynthetic studies on bone marrow cells from three patients with macroglobulinemia whose sera contained 7S IgM and 19S IgM. Labeled 7S IgM and 19S IgM were identified in extracellular culture fluids by radioimmunochemical techniques. The separation of the two molecular forms of IgM by density-gradient ultracentrifugation of the culture fluids before radioimmunochemical analyses permitted the identification of both the labeled 7S IgM and 19S IgM. One patient's serum contained two separate and distinct 19S IgM proteins as well as 7S IgM. The use of specific isolated carrier IgM proteins permitted the radioimmunochemical detection of labeled 7S IgM and both 19S IgM proteins. The introduction of cycloheximide into a culture system effects the cessation of protein synthesis. The analyses of culture fluids harvested at timed intervals after the addition of cycloheximide revealed not only the stability of 19S IgM to intracellular proteolysis, but also provided evidence for a possible precursor-product relationship between the 7S IgM and the 19S IgM. The demonstration that the labeled 7S IgM is neither an in vitro breakdown product of 19S IgM nor a resultant of 19S IgM intracellular catabolism substantiated the synthetic origin of 7S IgM in human sera.