Abe M, Goto T, Kosaka M, Wolfenbarger D, Weiss D T, Solomon A
Department of Medicine, University of Tennessee Medical Center/Graduate School of Medicine, Knoxville 37920, USA.
Clin Exp Immunol. 1998 Feb;111(2):457-62. doi: 10.1046/j.1365-2249.1998.00487.x.
Free light chains (FLC) are a natural product of B lymphocytes and, as such, represent a quantifiable biomarker of cellular proliferation. Accurate measurement of the concentrations of these components in serum and urine provides a unique means of ascertaining B cell immunoglobulin synthesis during physiologic and, especially, pathologic states, where such information has important diagnostic and therapeutic implications. Previously, use of such quantitative assays has been limited due to the lack of potent serologic reagents specific for these components. We have immunized mice with kappa- and lambda-type monoclonal human light chains (Bence Jones proteins (BJP)) and have obtained monoclonal antibodies (MoAbs) that differentiate between unbound and bound light chains. These highly specific MoAbs were used to measure by ELISA the concentrations of FLC in the serum of 22 normal individuals and in urine from 16 of these subjects. The mean serum kappa and lambda FLC concentrations were found to be 16.6+/-6.1 microg/ml and 33.8+/-14.8 microg/ml, respectively. In contrast, the values for urinary kappa and lambda FLC were 2.96+/-1.84 microg/ml and 1.07+/-0.69 microg/ml, respectively. In each case studied, the serum kappa:lambda ratio was consistently less than that of urine (mean values, serum approximately 1:2; urine approximately 3:1). That the rate of synthesis of lambda-type FLC exceeded that of kappa was evidenced in assays of culture fluid supernatants of unstimulated normal peripheral blood mononuclear cells (PBMC), where the mean kappa:lambda ratio was determined to be 1:1.4. Metabolic studies in which mice were injected with pools of kappa- and lambda-type BJP prepared in ratios of 1:1, 1:2 and 1:4 demonstrated that, regardless of the proportion, kappa FLC were preferentially excreted. Our studies provide the first evidence that lambda FLC are secreted by normal PBMC at a greater rate than are kappa FLC, as evidenced in biosynthetic studies and by measurement of their serum concentrations. Further, we posit that quaternary structural differences between the two light-chain isotypes may account for the predominance of kappa versus lambda components in urine.
游离轻链（FLC）是B淋巴细胞的天然产物，因此代表了一种可量化的细胞增殖生物标志物。准确测量血清和尿液中这些成分的浓度提供了一种独特的方法，用于确定生理状态尤其是病理状态下B细胞免疫球蛋白的合成情况，而这些信息具有重要的诊断和治疗意义。以前，由于缺乏针对这些成分的有效血清学试剂，此类定量检测的应用受到限制。我们用κ型和λ型单克隆人轻链（本斯·琼斯蛋白（BJP））免疫小鼠，并获得了能区分游离轻链和结合轻链的单克隆抗体（MoAb）。这些高度特异性的MoAb用于通过ELISA法测量22名正常个体血清和其中16名受试者尿液中的FLC浓度。发现血清κ和λ FLC的平均浓度分别为16.6±6.1μg/ml和33.8±14.8μg/ml。相比之下，尿液中κ和λ FLC的值分别为2.96±1.84μg/ml和1.07±0.69μg/ml。在所研究的每种情况下，血清κ:λ比值始终低于尿液中的比值（平均值，血清约为1:2；尿液约为3:1）。在未刺激的正常外周血单个核细胞（PBMC）培养液上清液的检测中，λ型FLC的合成速率超过κ型，其中κ:λ平均比值确定为1:1.4。在代谢研究中，给小鼠注射以1:1、1:2和1:4比例制备的κ型和λ型BJP混合物，结果表明，无论比例如何，κ FLC都优先被排泄。我们的研究首次证明，如生物合成研究及其血清浓度测量所示，正常PBMC分泌λ FLC的速率高于κ FLC。此外，我们推测两种轻链同种型之间的四级结构差异可能是尿液中κ成分相对于λ成分占优势的原因。
