微生物 免疫学

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。
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hnRNALL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。（生物谷Bioon.com）
生物谷推荐原始出处：
Immunity,19 December 2008 doi:10.1016/j.immuni.2008.11.004
Memory T Cell RNA Rearrangement Programmed by Heterogeneous Nuclear Ribonucleoprotein hnRNPLL
Zuopeng Wu1,Xinying Jia2,Laura de la Cruz2,Xun-Cheng Su2,Bruz Marzolf3,Pamela Troisch3,Daniel Zak3,Adam Hamilton1,Belinda Whittle1,Di Yu1,Daniel Sheahan1,Edward Bertram1,Alan Aderem3,Gottfried Otting2,Christopher C. Goodnow1,4,,andGerard F. Hoyne1,4
1 John Curtin School of Medical Research, Australian Phenomics Facility, Australian National University, Canberra ACT 0200, Australia2 Research School of Chemistry, Australian National University, Canberra ACT 0200, Australia3 Institute for Systems Biology, 1441 North 34th St., Seattle, WA 98103-9804, USACorresponding author4 These authors contributed equally
Summary
Differentiation of memory cells involves DNA-sequence changes in B lymphocytes but is less clearly defined in Tcells. RNA rearrangement is identified here as a key event in memory Tcell differentiation by analysis of a mouse mutation that altered the proportions of naive and memory Tcells and crippled the process of Ptprc exon silencing needed to generate CD45RO in memory Tcells. A single substitution ina 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 Tcell accumulation in peripheral lymphoid tissues but not proliferation. Exon-array analysis of Hnrpll mutant naive and memory Tcells revealed an extensive program of alternative mRNA splicing in memory Tcells, coordinated by hnRNPLL. A remarkable overlap with alternative splicing in neural tissues may reflect a co-opted strategy for diversifying memory Tcells.