Bothwell A L, Paskind M, Schwartz R C, Sonenshein G E, Gefter M L, Baltimore D
Nature. 1981 Mar 5;290(5801):65-7. doi: 10.1038/290065a0.
The expression of two kappa light chain immunoglobulins in the MPC-11 mouse myeloma is well established, the two protein products being apparently from RNA transcripts derived from separate, rearranged kappa alleles in the MPC-11 genome. Recently, the characterization of kappa-related RNAs and protein products in several lambda-producing myelomas has indicated that multiple expression of light chain RNAs is a common event in myelomas and other cells of the B-lymphocyte lineage. These studies suggest that, although many light chain alleles may function to make RNA and protein in a given B-lymphocytic cell, only one complete, functional light chain is generally translated from the RNAs present in a single cell. The myeloma, MOPC-315, synthesizes and secretes an antibody which has an alpha heavy chain and a lambda II light chain. The DNA of MOPC-315 either has no kappa genes or has only a fragment of one, but it certainly has no kappa genes in the embryonic configuration. Rearrangement of its lambda genes has been observed but the exact nature of the rearrangement is not known. Because initial observations suggested that an immunoglobulin-related protein other than alpha and lambda II was present in MOPC-315 cells, we undertook to derive molecular cDNA clones from the MRNA in MOPC-315 tumour cells. Analysis of the clones has now identified two lambda chain mRNA species: a normal lambda II chain mRNA and another which directs the synthesis of a deleted form of a lambda I protein. The nucleotide sequence of the deleted lambda I mRNA shows that it resulted from a joining of the sequence encoding amino acid 31 of the variable region directly to the constant region coding sequence.
MPC - 11小鼠骨髓瘤中两种κ轻链免疫球蛋白的表达已得到充分证实,这两种蛋白质产物显然来自于MPC - 11基因组中不同的、重排的κ等位基因产生的RNA转录本。最近,对几种产生λ链的骨髓瘤中κ相关RNA和蛋白质产物的特征分析表明,轻链RNA的多重表达在骨髓瘤和B淋巴细胞系的其他细胞中是常见现象。这些研究表明,尽管在给定的B淋巴细胞中许多轻链等位基因可能发挥作用产生RNA和蛋白质,但通常只有一条完整的、有功能的轻链从单个细胞中存在的RNA翻译而来。骨髓瘤MOPC - 315合成并分泌一种具有α重链和λII轻链的抗体。MOPC - 315的DNA要么没有κ基因,要么只有一个片段,但肯定没有处于胚胎构型的κ基因。已观察到其λ基因发生重排,但重排的确切性质尚不清楚。由于最初的观察表明MOPC - 315细胞中存在除α和λII之外的一种免疫球蛋白相关蛋白,我们着手从MOPC - 315肿瘤细胞的mRNA中获得分子cDNA克隆。对这些克隆的分析现已鉴定出两种λ链mRNA:一种是正常的λII链mRNA,另一种指导合成一种缺失形式的λI蛋白。缺失的λI mRNA的核苷酸序列表明,它是由可变区编码氨基酸31的序列直接与恒定区编码序列连接而成。