Gebert Claudia, Correia Lauren, Li Zhenhu, Petrie Howard T, Love Paul E, Pfeifer Karl
Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.
The Scripps Research Institute, Jupiter, FL, USA.
Immunol Cell Biol. 2017 May;95(5):473-477. doi: 10.1038/icb.2017.1. Epub 2017 Feb 28.
V-(D)-J recombination generates the antigen receptor diversity necessary for immune cell function, while allelic exclusion ensures that each cell expresses a single antigen receptor. V-(D)-J recombination of the Ig, Tcrb, Tcrg and Tcrd antigen receptor genes is ordered and sequential so that only one allele generates a productive rearrangement. The mechanism controlling sequential rearrangement of antigen receptor genes, in particular how only one allele is selected to initiate recombination while at least temporarily leaving the other intact, remains unresolved. Genomic imprinting, a widespread phenomenon wherein maternal or paternal allele inheritance determines allele activity, could represent a regulatory mechanism for controlling sequential V-(D)-J rearrangement. We used strain-specific single-nucleotide polymorphisms within antigen receptor genes to determine if maternal vs paternal inheritance could underlie chromosomal choice for the initiation of recombination. We found no parental chromosomal bias in the initiation of V-(D)-J recombination in T or B cells, eliminating genomic imprinting as a potential regulator for this tightly regulated process.
V-(D)-J重排产生免疫细胞功能所需的抗原受体多样性,而等位基因排斥确保每个细胞只表达一种抗原受体。免疫球蛋白、Tcrb、Tcrg和Tcrd抗原受体基因的V-(D)-J重排是有序且连续的,因此只有一个等位基因会产生有效的重排。控制抗原受体基因连续重排的机制,特别是如何只选择一个等位基因启动重排而至少暂时使另一个等位基因保持完整,仍未得到解决。基因组印记是一种广泛存在的现象,其中母本或父本等位基因的遗传决定等位基因的活性,它可能代表一种控制V-(D)-J连续重排的调节机制。我们利用抗原受体基因内的菌株特异性单核苷酸多态性来确定母本与父本遗传是否可能是重组起始时染色体选择的基础。我们发现在T细胞或B细胞中V-(D)-J重排起始时不存在亲代染色体偏向,排除了基因组印记作为这一严格调控过程潜在调节因子的可能性。