Bence Jones proteins and light chains of immunoglobulins. XI. A transient Bence Jones-related protein associated with corticosteroid therapy.

Abstract

A B S T R A C T Urine specimens from patients with multiple myeloma and Bence Jones proteinuria frequently contain low molecular weight proteins which correspond either to the amino-terminal, variant half (VL) Biosynthetic studies were performed with plasma cells derived from the bone marrow of this patient at a time when both the CL* and the Bence Jones protein were being excreted; both proteins were identified in extracellular culture fluid by immunochemical techniques. Whether the CL* is of synthetic or catabolic origin is presently not known; however, the detection of the CL* and the absence of any detectable protein related to the VL in the extracellular culture fluid might imply a synthetic origin of the CL* and suggest a corticosteroidinduced alteration in light chain synthesis.

Bence Jones Proteins and Light Chains of Immunoglobulins

“…6 We have found that 6 A receptor protein of high affinity and specificity for the corticosteroid dexamethasone has been demonstrated in plasma cells from the established X Bence Jones protein-synthesizing plasma cell tumor line of patient KIR (see Results) contain receptor protein of high binding affinity for dexamethasone;7 it remains to be established whether the observed differences in the effect of corticosteroids on Bence Jones protein or immunoglobulin synthesis (5-7) reflect quantitative or qualitative differences in glucocorticoid-receptor proteins among clones of plasma cells. The formation of CL* components, noted in three patients, may signify yet another effect of the putative corticosteroid-receptor protein complex on transcription of plasma cell messenger RNA, although a catabolic origin of these proteins cannot be excluded (8). Because the concentrations of prednisone used in the biosynthetic studies were several orders of magnitude greater than that required in other systems for controlling protein synthesis via receptor complexing and transcriptional control, the corticosteroid-associated alterations of Bence Jones protein synthesis may have resulted from other known biochemical effects of corticosteroids, e.g., on lysosomal and other membranes (1).…”

“…This component was detected by immunoelectrophoretic analysis 5 days after treatment was initiated (Fig. 6B); it increased in concentration by day 7, and could not be detected 24 The amino-terminus of CL* from patient EDW differed from those of CL* from patients WMS and OAK which corresponded to positions 92 and 97/106, respectively, of the K light polypeptide chain (8 (20,21). However, it seems unlikely that the marked decrease in Bence Jones proteinuria associated with chemotherapy resulted from an increased catabolic rate or a decreased proteinuric rate.…”

“…Previously, we reported that the intermittent administration of corticosteroids as part of a therapeutic regimen for a patient with multiple myeloma (a B cell neoplasm) resulted in an immediate and marked reduction in Bence Jones proteinuria and, concomitantly, in the excretion of a low molecular weight protein related to the carboxyl-terminal half (constant region) of the Bence Jones protein polypep-tide chain (8). This phenomenon was observed in several additional patients, but other types of responses were noted among patients treated in similar fashion.…”

“…Subclassification of K Bence Jones proteins as KI, KII, KIII, or KIV and of X Bence Jones proteins as XI, XII/XIII, or XIV was determined by immunodiffusion analyses with antisera of known specificity (11,12). 1 The protein concentration of urine specimens was measured by a sulfosalicylic acid turbidity method (8) and that of serum specimens by refractometry. The amount of Bence Jones protein relative to other urinary proteins and the concentration of serum myeloma protein were determined by cellulose acetate electrophoresis and densitometry (10).…”

A molecular basis for nonsecretory myeloma

“…Undiluted samples also were examined in similar fashion, as were unconcentrated urine specimens and 24-hour collections that had been dialyzed extensively against distilled water, lyophilized, and reconstituted to a protein concentration of 100 mg/mL. 10 …”