最新Immunity封面文章

　　

生物通报道，澳大利亚国立大学医学研究所，化学研究所的科学家发现新的免疫理论，相关成果公布在最新一期的Immunity上，并列为封面文章。

 

众所周知，B细胞具有记忆性，一般来说B细胞的记忆性的形成与DNA序列的改变有联系，B细胞通过改变DNA序列来维持细胞的记忆性。但是，免疫细胞的记忆性机制研究比较多的是B细胞，相比之下，T细胞研究的比较少。

 

本研究的领导者，Christopher C.Goodnow将在该文章中讲述T细胞的记忆机制。研究小组发现，记忆性T细胞的分化过程中，RNA重排起重要作用。研究小组以小鼠的研究模型，通过沉默一个记忆性T细胞分化的关键基因ptprc（是产生记忆性T细胞CD45RO的重要基因），结果发现记忆性T细胞的比例发生改变。并且RNA结合蛋白hnRNPLL发生改变，会导致RNA的识别区域变得不稳定。

 

研究者发现hnrpll突变会导致T细胞不在外周淋巴结聚集，但不影响增殖。对这些突变细胞进行外显子检测分析，结果发现记忆性T细胞的mRNA剪接过程发生的广泛的改变。并且相同的变化还出现在神经组织中，这可能是引发记忆性T细胞发生变化的原因。

 

原文摘要：Memory T Cell RNA Rearrangement Programmed by Heterogeneous Nuclear Ribonucleoprotein hnRNPLL

【Summary】

Differentiation of memory cells involves DNA-sequence changes in B lymphocytes but is less clearly defined in T cells. RNA rearrangement is identified here as a key event in memory T cell differentiation by analysis of a mouse mutation that altered the proportions of naive and memory T cells and crippled the process of Ptprc exon silencing needed to generate CD45RO in memory T cells. A single substitution in a memory-induced RNA-binding protein, hnRNPLL, destabilized an RNA-recognition domain that bound with micromolar affinity to RNA containing the Ptprc exon-silencing sequence. Hnrpll mutation selectively diminished T cell accumulation in peripheral lymphoid tissues but not proliferation. Exon-array analysis of Hnrpll mutant naive and memory T cells revealed an extensive program of alternative mRNA splicing in memory T cells, coordinated by hnRNPLL. A remarkable overlap with alternative splicing in neural tissues may reflect a co-opted strategy for diversifying memory T cells.