Sakamoto S, Mathieson B J, Komschlies K L, Bhat N K, Young H A
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21701-1013.
Eur J Immunol. 1989 May;19(5):873-9. doi: 10.1002/eji.1830190514.
Previous analyses of T cell receptor beta chain (TcR beta) genomic DNA from subsets of human peripheral blood leukocytes suggested that the TcR beta methylation pattern might reflect distinct differentiation pathways. The studies presented here, using murine thymocyte subsets, have specifically addressed the question of whether methylation of TcR beta DNA is related to the cellular maturity and type of TcR beta mRNA expressed in the different subsets. We have observed that the DNA isolated from either CD4+ or CD8+ thymocytes, the more mature thymic subsets, is less methylated in the TcR beta region than DNA isolated from the CD4-CD8-, double-negative population containing the more immature thymocytes. In addition, this pattern of DNA methylation is directly related to the ratio of 1.3-kb to 1.0-kb TcR beta mRNA seen in these different cell types. Although a quantitative difference in the level of TcR beta mRNA was noted for the two mature subsets, no qualitative difference in the ratio of 1.3-kb to 1.0-kb mRNA was detected. Furthermore, these DNA methylation patterns appear to be lineage related, because the TcR beta region of genomic DNA isolated from mouse macrophages is heavily methylated.
先前对人外周血白细胞亚群的T细胞受体β链(TcRβ)基因组DNA的分析表明,TcRβ甲基化模式可能反映了不同的分化途径。本文利用小鼠胸腺细胞亚群进行的研究,专门探讨了TcRβ DNA甲基化是否与不同亚群中表达的TcRβ mRNA的细胞成熟度和类型相关的问题。我们观察到,从更成熟的胸腺亚群CD4 +或CD8 +胸腺细胞中分离的DNA,在TcRβ区域的甲基化程度低于从含有更不成熟胸腺细胞的CD4 - CD8 -双阴性群体中分离的DNA。此外,这种DNA甲基化模式与这些不同细胞类型中所见的1.3 kb与1.0 kb TcRβ mRNA的比例直接相关。尽管在两个成熟亚群中注意到TcRβ mRNA水平存在定量差异,但未检测到1.3 kb与1.0 kb mRNA比例的定性差异。此外,这些DNA甲基化模式似乎与谱系相关,因为从小鼠巨噬细胞中分离的基因组DNA的TcRβ区域高度甲基化。