Webb C F, Cooper M D, Burrows P D, Griffin J A
Proc Natl Acad Sci U S A. 1985 Aug;82(16):5495-9. doi: 10.1073/pnas.82.16.5495.
During differentiation B lymphocytes may switch from the expression of surface IgM to the synthesis of IgG, IgA, or IgE isotypes by using a different heavy chain constant region (CH) gene. The molecular mechanisms by which switching occurs remain controversial. Rearrangements and deletions of CH genes 5' to the expressed gene have often been observed in the mouse and, more recently, in human cells that have switched isotypes. We have used human JH, C micro, C gamma, and C alpha probes to examine the extent of the deletions and rearrangements in clones of Epstein-Barr virus-transformed human cells that produce IgG1, IgG3, IgG4, or IgA1. Though deletions of CH genes 5' to the expressed CH gene were consistently observed, the rearrangement process appeared to be highly variable for the nonproductive CH gene locus: deletion or persistence of 5' CH genes, combinations of deletion and duplication of 5' genes, and deletions extending to 3' CH genes. Our results reveal an unexpected lack of specificity in the DNA deletions in cells that have undergone isotype switching.
在分化过程中，B淋巴细胞可能通过使用不同的重链恒定区（CH）基因，从表面IgM的表达转换为IgG、IgA或IgE同种型的合成。发生转换的分子机制仍存在争议。在小鼠中，最近在已经发生同种型转换的人类细胞中，经常观察到已表达基因5'端CH基因的重排和缺失。我们使用人JH、Cμ、Cγ和Cα探针，来检测产生IgG1、IgG3、IgG4或IgA1的爱泼斯坦-巴尔病毒转化的人类细胞克隆中的缺失和重排程度。虽然始终观察到已表达CH基因5'端的CH基因缺失，但对于无功能的CH基因座，重排过程似乎高度可变：5' CH基因的缺失或保留、5'基因缺失和重复的组合，以及延伸至3' CH基因的缺失。我们的结果揭示了在经历同种型转换的细胞中，DNA缺失意外地缺乏特异性。
