Distinct signal thresholds for the unique antigen receptor-linked gene expression programs in mature and immature B cells
Distinct signal thresholds for the unique antigen receptor-linked gene expression programs in mature and immature B cells
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DOI：
10.1084/jem.190.6.749
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发表时间：
1999-09-20
影响因子：
15.3
通讯作者：
Cambier, JC
中科院分区：
文献类型：
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作者：
Benschop, RJ;Melamed, D;Cambier, JC
虽然已经确定未成熟的B淋巴细胞与其成熟的对应物相比对耐受诱导非常敏感，但这种差异的分子基础尚不清楚。我们证明了B细胞抗原受体的信号传导导致成熟和未成熟B细胞中不同且相互排斥的生物学反应：成熟细胞中CD86、CD69和MHC II类的上调以及未成熟细胞中的受体编辑。这些反应可以简单地通过升高细胞内游离钙水平来诱导，如在受体聚集后发生的。重要的是，诱导未成熟B细胞应答需要比诱导成熟B细胞应答小得多的细胞内游离钙的增加。对细胞内游离钙的生物反应和敏感性的这些差异可能有助于在未成熟阶段选择性消除甚至那些对自身抗原表达低亲和力的B细胞。
Although it is well established that immature B lymphocytes are exquisitely sensitive to tolerance induction compared with their mature counterparts, the molecular basis for this difference is unknown. We demonstrate that signaling by B cell antigen receptors leads to distinct and mutually exclusive biologic responses in mature and immature B cells: upregulation of CD86, CD69, and MHC class II in mature cells and receptor editing in immature cells. These responses can be induced simply by elevation of intracellular free calcium levels, as occurs after receptor aggregation. Importantly, induction of immature B cell responses requires much smaller increases in intracellular free calcium than does induction of mature B cell responses. These differences in biologic response and sensitivity to intracellular free calcium likely contributes to selective elimination at the immature stage of even those B cells that express low affinity for self-antigens.