Components of the antigen processing and presentation pathway revealed by gene expression microarray analysis following B cell antigen receptor (BCR) stimulation.
Components of the antigen processing and presentation pathway revealed by gene expression microarray analysis following B cell antigen receptor (BCR) stimulation.
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DOI：
10.1186/1471-2105-7-237
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发表时间：
2006-05-02
影响因子：
3
通讯作者：
Alliance for Cellular Signaling
中科院分区：
文献类型：
--
作者：
Lee JA;Sinkovits RS;Mock D;Rab EL;Cai J;Yang P;Saunders B;Hsueh RC;Choi S;Subramaniam S;Scheuermann RH;Alliance for Cellular Signaling
细胞外配体如抗原、脂多糖和CD40配体激活幼稚B淋巴细胞，通过复杂的信号转导途径引起共同的和配体特异性的表型变化。例如，虽然这三种配体都能促进增殖，但只有通过B细胞抗原受体(BCR)的刺激才能诱导静止的脾B细胞发生凋亡。为了确定对配体刺激的共同和独特的生物学反应，我们使用cDNA微阵列和统计方法CLASTFI(生物推断的聚类分配)比较了一组配体在正常的原代B细胞中诱导的基因表达变化，该方法确定了具有相似基因本体论™注释的基因的显著共同聚集性。分类分析显示，在BCR特异性基因簇中，参与离子和囊泡运输的基因过度表达，包括质子泵的多个组成部分，这表明抗原处理和提呈途径的激活是对抗原受体刺激的主要生物学反应。在后续实验中，没有包括在初始微阵列数据集中的质子泵组件也被上调，以响应BCR刺激。在BCR刺激下，MHC-II类分子的表达被特异性地维持。此外，BCR的配体特异性内化是B细胞抗原处理和呈递的第一步，被证明。这些观察结果提供了在分类函数中实现的计算方法的实验验证，表明基于分类函数的基因表达聚类分析是识别与实验条件变量相关的生物过程的有效数据挖掘工具。此外，这项分析已经确定了B细胞抗原加工和提呈途径的至少38个候选成分，并为未来的研究奠定了基础，这些研究侧重于更好地了解B细胞抗原加工和提呈所涉及的成分和独特的成分。
Activation of naïve B lymphocytes by extracellular ligands, e.g. antigen, lipopolysaccharide (LPS) and CD40 ligand, induces a combination of common and ligand-specific phenotypic changes through complex signal transduction pathways. For example, although all three of these ligands induce proliferation, only stimulation through the B cell antigen receptor (BCR) induces apoptosis in resting splenic B cells. In order to define the common and unique biological responses to ligand stimulation, we compared the gene expression changes induced in normal primary B cells by a panel of ligands using cDNA microarrays and a statistical approach, CLASSIFI (Cluster Assignment for Biological Inference), which identifies significant co-clustering of genes with similar Gene Ontology™ annotation. CLASSIFI analysis revealed an overrepresentation of genes involved in ion and vesicle transport, including multiple components of the proton pump, in the BCR-specific gene cluster, suggesting that activation of antigen processing and presentation pathways is a major biological response to antigen receptor stimulation. Proton pump components that were not included in the initial microarray data set were also upregulated in response to BCR stimulation in follow up experiments. MHC Class II expression was found to be maintained specifically in response to BCR stimulation. Furthermore, ligand-specific internalization of the BCR, a first step in B cell antigen processing and presentation, was demonstrated. These observations provide experimental validation of the computational approach implemented in CLASSIFI, demonstrating that CLASSIFI-based gene expression cluster analysis is an effective data mining tool to identify biological processes that correlate with the experimental conditional variables. Furthermore, this analysis has identified at least thirty-eight candidate components of the B cell antigen processing and presentation pathway and sets the stage for future studies focused on a better understanding of the components involved in and unique to B cell antigen processing and presentation.
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DOI：
10.1073/pnas.2536699100
发表时间：
2003-12-23
影响因子：
11.1
作者：
Duffield, A;Kamsteeg, EJ;Caplan, MJ
通讯作者：
Caplan, MJ
影响因子：
3.6
作者：
Chu, CC;Paul, WE
通讯作者：
Paul, WE
影响因子：
32.4
作者：
Healy, JI;Dolmetsch, RE;Goodnow, CC
通讯作者：
Goodnow, CC
影响因子：
4.4
作者：
Ha, YJ;Lee, JR
通讯作者：
Lee, JR
影响因子：
4.8
作者：
Brown, BK;Li, C;Song, WX
通讯作者：
Song, WX