Kong Q, Zhao L, Subbaiah S, Maizels N
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
J Immunol. 1998 Jul 1;161(1):294-301.
Somatic hypermutation is a highly regulated process that targets mutations to the rearranged Ig genes. Little is known about the cis-elements required for somatic hypermutation of the lambda light chain gene. We have studied somatic hypermutation of a rearranged lambda 1 transgene under the control of either a lambda 2-4 or kappa 3' enhancer. The mutations in the transgenes were analyzed by sequencing DNA amplified from hypermutating Peyer's patch B cells. The results indicate that the lambda 3' enhancer can drive active hypermutation of a lambda 1 transgene in Peyer's patch cells. The lambda 1 transgene under analysis carried two marked V lambda 2 genes immediately upstream that could serve as sequence donors in possible gene conversion events. There was no evidence of sequence transfer to the hypermutated lambda 1 gene, suggesting that gene conversion is not a major mechanism for somatic hypermutation in mice.
体细胞高频突变是一个高度调控的过程，它将突变靶向重排的免疫球蛋白基因。关于λ轻链基因体细胞高频突变所需的顺式元件，人们了解甚少。我们研究了在λ2-4或κ3'增强子控制下重排的λ1转基因的体细胞高频突变。通过对从发生高频突变的派尔集合淋巴结B细胞中扩增的DNA进行测序，分析转基因中的突变。结果表明，λ3'增强子可驱动派尔集合淋巴结细胞中λ1转基因的活跃高频突变。所分析的λ1转基因在紧邻上游携带两个标记的Vλ2基因，它们可能在潜在的基因转换事件中作为序列供体。没有证据表明序列转移到了高频突变的λ1基因，这表明基因转换不是小鼠体细胞高频突变的主要机制。
