Kinetics of B cell receptor signaling in human B cell subsets mapped by phosphospecific flow cytometry
Kinetics of B cell receptor signaling in human B cell subsets mapped by phosphospecific flow cytometry
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DOI：
10.4049/jimmunol.177.3.1581
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发表时间：
2006-08-01
影响因子：
4.4
通讯作者：
Levy, Ronald
中科院分区：
文献类型：
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作者：
Irish, Jonathan M.;Czerwinski, Debra K.;Levy, Ronald
BCR信号传导的差异可能决定增殖和细胞死亡等多种结果。我们用流式细胞术分析了原代人B细胞亚群中的BCR信号动力学。在表达IgM的优势群体中，BCR交联导致Syk、ERK1/2和p38信号的快速爆发。相反，随着时间的推移，IgG B细胞维持较高的每细胞ERKI/2磷酸化。这种二分法提示了一种抑制IgM传递信号的机制。IgM B细胞的调节性磷酸酶活性是由bcr介导的，其启动速度比激酶活性慢。这种BCR介导的磷酸酶活性对H2O2的抑制很敏感，并且需要减弱IgM BCR信号。这些结果提供了人类原代B细胞亚群中BCR信号传导的第一个动力学图谱，并为B细胞疾病（如自身免疫和癌症）信号传导的新研究提供了可能。
Differences in BCR signaling may govern outcomes as diverse as proliferation and cell death. We profiled BCR signaling kinetics in subsets of primary human B cells using flow cytometry. In the predominant population expressing IgM, BCR cross-linking led to a quick burst of Syk, ERK1/2, and p38 signaling. In contrast, IgG B cells sustained higher per-cell ERKI/2 phosphorylation over time. This dichotomy suggested a mechanism for dampening signals transmitted by IgM. Regulatory phosphatase activity in IgM B cells was BCR-mediated and initiated more slowly than kinase activity. This BCR-mediated phosphatase activity was sensitive to inhibition by H2O2, and required to attenuate IgM BCR signaling. These results provide the first kinetic maps of BCR signaling in primary human B cell subsets and enable new studies of signaling in B cell disorders, such as autoimmunity and cancer.