Dunnick W, Wilson M, Stavnezer J
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109-0620.
Mol Cell Biol. 1989 May;9(5):1850-6. doi: 10.1128/mcb.9.5.1850-1856.1989.
The heavy-chain switch from immunoglobulin M (IgM) expression to IgA expression is mediated by a recombination event between segments of DNA called switch regions. The switch regions lie two to six kilobases upstream of the mu and alpha constant region coding segments. Switch recombination to IgA expression results in a recombinant mu-alpha switch region upstream of the expressed alpha constant region gene. We have characterized the products of switch recombination by a lymphoma cell line, I.29. Two sets of molecular clones represent the expected products of simple mu to alpha switches. Five members of a third set of molecular clones share the same recombination site in both the mu and the alpha switch regions, implying that the five molecular clones were derived from a single switch recombination event. Surprisingly, the five clones fall into two sets of sequences, which differ from each other by several point mutations and small deletions. Duplication of switch region sequences are also found in these five molecular clones. An explanation for these data is that switch recombination involves DNA synthesis, which results in nucleotide substitutions, small deletions, and duplications.
免疫球蛋白重链从免疫球蛋白M(IgM)表达向IgA表达的转换是由称为转换区的DNA片段之间的重组事件介导的。转换区位于μ链和α链恒定区编码片段上游2至6千碱基处。向IgA表达的转换重组导致在表达的α链恒定区基因上游出现重组的μ-α转换区。我们通过淋巴瘤细胞系I.29对转换重组的产物进行了表征。两组分子克隆代表了简单的μ链到α链转换的预期产物。第三组分子克隆中的五个成员在μ链和α链转换区具有相同的重组位点,这意味着这五个分子克隆源自单个转换重组事件。令人惊讶的是,这五个克隆分为两组序列,它们彼此之间存在几个点突变和小的缺失差异。在这五个分子克隆中还发现了转换区序列的重复。对这些数据的一种解释是,转换重组涉及DNA合成,这会导致核苷酸替换、小的缺失和重复。