Gorman J R, van der Stoep N, Monroe R, Cogne M, Davidson L, Alt F W
Howard Hughes Medical Institute, The Children's Hospital, Boston, Massachusetts 02115, USA.
Immunity. 1996 Sep;5(3):241-52. doi: 10.1016/s1074-7613(00)80319-2.
We generated mice harboring germline mutations in which the enhancer element located 9 kb 3' of the immunoglobulin kappa light chain gene (3'E kappa) was replaced either by a single loxP site (3'E kappa delta) or by a neomycin resistance gene (3'E kappa N). Mice homozygous for the 3'E(kappa delta) mutation had substantially reduced numbers of kappa-expressing B cells and increased numbers of lambda-expressing B cells accompanied by decreased kappa versus lambda gene rearrangement. In these mutant mice, kappa expression was reduced in resting B cells, but was normal in activated B cells. The homozygous 3'E(kappa)N mutation resulted in a similar but more pronounced phenotype. Both mutations acted in cis. These studies show that the 3'E(kappa) is critical for establishing the normal kappa/lambda ratio, but is not absolutely essential for kappa gene rearrangement or, surprisingly, for normal kappa expression in activated B cells. These studies also imply the existence of additional regulatory elements that have overlapping function with the 3'E(kappa) element.
我们构建了在种系中发生突变的小鼠，其中位于免疫球蛋白κ轻链基因（3'Eκ）3'端9 kb处的增强子元件被单个loxP位点（3'Eκδ）或新霉素抗性基因（3'EκN）取代。3'E（κδ）突变纯合子小鼠中，表达κ的B细胞数量大幅减少，表达λ的B细胞数量增加，同时κ与λ基因重排减少。在这些突变小鼠中，静止B细胞中的κ表达降低，但活化B细胞中的κ表达正常。纯合3'E（κ）N突变导致类似但更明显的表型。两种突变均顺式作用。这些研究表明，3'E（κ）对于建立正常的κ/λ比例至关重要，但对于κ基因重排并非绝对必要，令人惊讶的是，对于活化B细胞中的正常κ表达也不是绝对必要的。这些研究还暗示存在与3'E（κ）元件功能重叠的其他调控元件。
