FC RECEPTOR PHOSPHORYLATION DURING RECEPTOR-MEDIATED CONTROL OF B-CELL ACTIVATION
FC RECEPTOR PHOSPHORYLATION DURING RECEPTOR-MEDIATED CONTROL OF B-CELL ACTIVATION
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DOI：
10.1038/345628a0
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发表时间：
1990-06-14
期刊：
影响因子：
64.8
通讯作者：
MELLMAN, I
中科院分区：
文献类型：
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作者：
HUNZIKER, W;KOCH, T;MELLMAN, I
众所周知，巨噬细胞上IgG的Fc受体（FcRII）介导抗体-抗原复合物的内吞作用，并发出炎症和细胞毒性物质释放的信号1。FcRII也在B细胞上以高水平表达，其中与通过膜免疫球蛋白调节B细胞活化相比，FcRII较少参与内吞作用2，3。尽管膜免疫球蛋白的交联可通过刺激磷脂酶C、细胞内Ca 2+的动员和蛋白激酶C的活化导致B细胞分化和增殖，但FcR与膜免疫球蛋白的交联赋予了阻止或中止活化的显性抑制信号2 -6。这种形式的调节可能有一个作用，在诱导耐受性的IgG 7和控制B细胞库的抗独特型8，9。FcR在B细胞和巨噬细胞上的不同功能可能反映了这些细胞类型表达密切相关但不同的FcR同种型的事实。我们最近发现，主要的淋巴细胞FcR同种型FcRII-B1由于在其胞质尾中的47个氨基酸的框内插入而不能通过包被的小凹和包被的囊泡介导内吞作用10，11。在这里，我们表明，这种插入，从FcRII-B2巨噬细胞亚型缺席，也包含丝氨酸磷酸化位点，可能有一个作用的能力，FcR通过膜免疫球蛋白调节B细胞活化。
IT is well known that Fc receptors for IgG (FcRII) on macrophages mediate the endocytosis of antibody–antigen complexes and signal the release of inflammatory and cytotoxic agents1. FcRII are also expressed at high levels on B cells where they are less involved in endocytosis than in modulating B-cell activation by membrane immunoglobulins2,3. Although crosslinking of membrane immunoglobulins can result in B-cell differentiation and proliferation through stimulation of phospholipase C, mobilization of intracellular Ca2+, and activation of protein kinase C, crosslinking FcR with membrane immunoglobulins confers a dominant inhibitory signal that prevents or aborts activation2–6. This form of regulation may have a role in the induction of tolerance by IgG7and in controlling the B-cell repertoire by anti-idiotypes8,9. The different functions of FcR on B cells and macrophages may reflect the fact that these cell types express closely related but distinct FcR isoforms. We have recently found that the main lymphocyte FcR isoform, FcRII-B1, is unable to mediate endocytosis by way of coated pits and coated vesicles owing to an in-frame insertion of 47 amino acids in its cytoplasmic tail10,11. Here we show that this insert, absent from the FcRII-B2 macrophage isoform, also contains serine phosphorylation sites that may have a role in the ability of FcR to regulate B-cell activation through membrane immunoglobulins.