In vitro kinetics of immunoglobulin synthesis and secretion by nonsecretory human myeloma cells

To characterize the defect in “nonsecretory” myeloma, and to relate it to the secretory phenomenon of human myeloma cells, plasma cells from such a patient were studied in vitro and compared with other myeloma cells. The cells had the morphologic appearance of plasma cells, and contained cytoplasmic IgA-λ, but lacked surface membrane Ig and were PAS-negative. The rough endoplasmic reticulum and Golgi apparatus were anatomically intact, but the endoplasmic reticulum was distended with proteinaceous material. Incorporation of 3 H-labeled leucine and carbohydrate precursors into Ig, as determined by immune coprecipitation, was measured for nonsecretory and secretory myeloma cells. Typical myeloma cells synthesized intracellular Ig, then actively secreted the newly synthesized protein into the medium. The nonsecretory cells synthesized Ig, though at a slower rate, but only released a small amount into the medium. The Ig released by these cells had a much higher 3 H-carbohydrate/ 3 H-leucine incorporation ratio than that released by the secretory myeloma cells. The data suggest that these cells have a block at the level of the Golgi apparatus, perhaps related to glycosylation, that prevents secretion. This finding may represent an abnormality induced during the malignant transformation or the clonal proliferation of a cell from a subpopulation of immunocyte precursors present normally in small numbers.