Lymphotoxin-β receptor-dependent genes in lymph node and follicular dendritic cell transcriptomes

Lymphotoxin-β receptor-dependent genes in lymph node and follicular dendritic cell transcriptomes
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DOI:
10.4049/jimmunol.174.9.5526
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发表时间:
2005-05-01
影响因子:
4.4
通讯作者:
Aguzzi, A
Aguzzi, A
中科院分区:
医学2区
文献类型:
--
作者:
Huber, C;Thielen, C;Aguzzi, A

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亲和力成熟和Ab类别转换发生在淋巴生发中心(GC),其中分化和维持依赖于光敏素(LT)信号传导,并且包括滤泡树突状细胞(FDC)的分化。导致FDC和GC成熟的事件定义不明确。使用功能基因组学的几种方法,我们列举了在小鼠中通过抑制LT β受体(LT β R)信号传导和/或在富含FDC的GC分离株中过度表达而受影响的转录本。对12个基因中的3个进行蛋白质表达分析,这3个基因都富集在FDC中,并通过LT β R信号转导抑制下调,验证了它们是FDC标记物。这三个之一,clusterin的功能分析表明,作为一个GC B细胞的FDC衍生的营养因子的作用。因此,在这项研究中提出的一组基因包括来自LT β R信号传导的标记物和与GC和FDC功能相关的转录物。
Affinity-maturation and Ab class switches occur in lymphoid germinal centers (GCs), in which differentiation and maintenance depend on lymphotoxin (LT) signaling and include differentiation of follicular dendritic cells (FDCs). The events leading to FDC and GC maturation are poorly defined. Using several approaches of functional genomics, we enumerated transcripts affected in mice by suppressing LT beta receptor (LT beta R) signaling and/or overrepresented in FDC-enriched GC isolates. Protein expression analysis of 3 of 12 genes both enriched in FDCs and down-regulated by LT beta R signaling suppression validated them as FDC markers. Functional analysis of one of these three, clusterin, suggests a role as an FDC-derived trophic factor for GC B cells. Hence, the set of genes presented in this study includes markers emanating from LT beta R signaling and transcripts relevant to GC and FDC function.