Cooperation of multiple signaling pathways in CD40-regulated gene expression in B lymphocytes.

Dadgostar Hajir; Zarnegar Brian; Hoffmann AlexanderQin XiaoFengTruong UyenRao GovindaBaltimore DavidCheng Genhong

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Cooperation of multiple signaling pathways in CD40-regulated gene expression in B lymphocytes.

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CD40/CD40L interaction is essential for multiple biological events in T dependent humoral immune responses, including B cell survival and proliferation, germinal center and memory B cell formation, and antibody isotype switching and affinity maturation. By using high-density microarrays, we examined gene expression in primary mouse B lymphocytes after multiple time points of CD40L stimulation. In addition to genes involved in cell survival and growth, which are also induced by other mitogens such as lipopolysaccharide, CD40L specifically activated genes involved in germinal center formation and T cell costimulatory molecules that facilitate T dependent humoral immunity. Next, by examining the roles of individual CD40-activated signal transduction pathways, we dissected the overall CD40-mediated response into genes independently regulated by the individual pathways or collectively by all pathways. We also found that gene down-regulation is a significant part of the overall response and that the p38 pathway plays an important role in this process, whereas the NF-kappa B pathway is important for the up-regulation of primary response genes. Our finding of overlapping independent control of gene expression modules by different pathways suggests, in principle, that distinct biological behaviors that depend on distinct gene expression subsets can be manipulated by targeting specific signaling pathways.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2002年第3期|1497-1502|共6页
作者
Dadgostar Hajir; Zarnegar Brian; Hoffmann AlexanderQin XiaoFengTruong UyenRao GovindaBaltimore DavidCheng Genhong;
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作者单位

Molecular Biology Institute and Medical Scientist Training Program, School of Medicine, University of California, Los Angeles, CA 90095, USA.;

itt.edu;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Antigens; CD40; B-Lymphocytes; Gene Expression Regulation; Signal Transduction; 抗原; B淋巴细胞; 基因表达调控; 信号传递;

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Cooperation of multiple signaling pathways in CD40-regulated gene expression in B lymphocytes.

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