Yu H, Eckhardt L A
Mol Cell Biol. 1986 Dec;6(12):4228-35. doi: 10.1128/mcb.6.12.4228-4235.1986.
The spontaneous mutation rate of immunoglobulin genes expressed in myeloma cells is well above that of other genes expressed in these or in other cell types. The nature of such mutations in one myeloma cell line, MPC11, was explored at the molecular level. Included in this study were MPC11 variants representing 24 independent and spontaneous mutations affecting immunoglobulin secretion. Of the mutants studied, 19 had ceased immunoglobulin heavy chain (IgH) production (nonproducers), and 5 produced from as little as 1/1,000 to as much as 1/10 the amount of immunoglobulin produced by MPC11 (low producers). Only one of the MPC11 mutants (a nonproducer) showed no evidence of DNA rearrangement in or near the expressed IgH gene. The formerly expressed gamma 2b gene had been deleted in 18 of the 19 nonproducers. All of the low producers had undergone DNA rearrangement in or near the expressed IgH gene, and three of them produced immunoglobulin of a new heavy chain class. The cause for reduced heavy-chain synthesis in the low producers is not yet known. However, in several of these mutants, the defect appeared to be posttranscriptional. In these cell lines, steady-state IgH mRNA levels were much lower than in the parent cell line, while the heavy-chain gene transcription rate remained unchanged.
骨髓瘤细胞中表达的免疫球蛋白基因的自发突变率远高于这些细胞或其他细胞类型中表达的其他基因。在分子水平上探究了一种骨髓瘤细胞系MPC11中此类突变的性质。本研究包括代表24个影响免疫球蛋白分泌的独立自发突变的MPC11变体。在所研究的突变体中，19个已停止产生免疫球蛋白重链（IgH）（无分泌者），5个产生的免疫球蛋白量仅为MPC11产生量的1/1000至1/10（低分泌者）。MPC11突变体中只有一个（无分泌者）在表达的IgH基因内部或附近未显示DNA重排的证据。19个无分泌者中有18个已缺失先前表达的γ2b基因。所有低分泌者在表达的IgH基因内部或附近都发生了DNA重排，其中三个产生了新重链类别的免疫球蛋白。低分泌者中重链合成减少的原因尚不清楚。然而，在其中一些突变体中，缺陷似乎是转录后水平的。在这些细胞系中，稳态IgH mRNA水平远低于亲本细胞系，而重链基因转录率保持不变。
