Solomon A, McLaughlin C L, Capra J D
J Clin Invest. 1975 Mar;55(3):579-86. doi: 10.1172/JCI107965.
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) or to the carboxyl-terminal, constant half (CL) of the Bence Jones protein. Analyses of urine specimens from such patients who had received high doses of corticosteroids as part of their treatment regimen revealed that concomitantly with a decrease in Bence Jones protein excretion was the appearance of a low molecular weight protein related to the Bence Jones protein but not identical to the VL or to the CL. Analyses of daily urine specimens obtained from one such patient over an extended time period revealed that a reproducible chain of events occurred during a treatment regimen which included oral administration of 75 mg of prednisone daily for 7 consecutive days. The amount of Bence Jones protein excreted decreased progressively, and by the 5th day was usually less than 10% of the pretreatment value. The urine specimen obtained on the 6th day of treatment was virtually devoid of Bence Jones protein but contained a newly appearing protein whose electrophoretic mobility was distinct from that of the Bence Jones protein or its VL or CL. Cessation of corticosteroid therapy resulted in a prompt disappearance of the new protein and in a progressive increase in the amount of Bence Jones protein excreted. The new protein was isolated from the urine of this patient and was purified for comparative studies with Bence Jones protein and with the VL and CL prepared by specific enzymatic cleavage of the Bence Jones protein. These studies revealed that the new protein was most related antigenically to the CL, but could be distinguished immunochemically from the CL. This new protein, a component found in vivo related to the constant half of the light polypeptide chain, was designated CL, and was structurally 25 amino acid residues longer than the CL, that is, the amino-terminus of the enzymatically prepared CL was at position 117 whereas that of the transitory new Bence Jones-related protein was at position 92 of the light polypeptide chain. 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 corticosteroid-induced alteration in light chain synthesis.
患有多发性骨髓瘤和本-周蛋白尿症患者的尿液标本中常常含有低分子量蛋白质，这些蛋白质要么对应于本-周蛋白的氨基末端可变半段（VL），要么对应于羧基末端恒定半段（CL）。对接受高剂量皮质类固醇作为治疗方案一部分的此类患者的尿液标本进行分析发现，随着本-周蛋白排泄量的减少，出现了一种与本-周蛋白相关但与VL或CL不同的低分子量蛋白质。对一名此类患者在较长时间段内每日采集的尿液标本进行分析发现，在一个包括连续7天每日口服75毫克泼尼松的治疗方案期间，发生了一系列可重复的事件。本-周蛋白的排泄量逐渐减少，到第5天时通常不到治疗前值的10%。治疗第6天采集的尿液标本实际上不含本-周蛋白，但含有一种新出现的蛋白质，其电泳迁移率与本-周蛋白或其VL或CL不同。停止皮质类固醇治疗导致新蛋白质迅速消失，本-周蛋白排泄量逐渐增加。从该患者尿液中分离出这种新蛋白质，并进行纯化，以便与本-周蛋白以及通过对本-周蛋白进行特异性酶切制备的VL和CL进行比较研究。这些研究表明，新蛋白质在抗原性上与CL最相关，但在免疫化学上可与CL区分开来。这种新蛋白质是体内发现的一种与轻多肽链恒定半段相关的成分，被命名为CL，其结构比CL长25个氨基酸残基，也就是说，酶法制备的CL的氨基末端位于轻多肽链的第117位，而短暂出现的与本-周蛋白相关的新蛋白质的氨基末端位于轻多肽链的第92位。在该患者骨髓来源的浆细胞同时分泌CL和本-周蛋白时进行了生物合成研究；通过免疫化学技术在细胞外培养液中鉴定出了这两种蛋白质。目前尚不清楚CL是合成来源还是分解代谢来源；然而，在细胞外培养液中检测到CL且未检测到任何与VL相关的可检测蛋白质，这可能意味着CL是合成来源，并提示皮质类固醇诱导了轻链合成的改变。
