Augmentation of signaling through BCR containing IgE but not that containing IgA due to lack of CD22-mediated signal regulation
Augmentation of signaling through BCR containing IgE but not that containing IgA due to lack of CD22-mediated signal regulation
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DOI：
10.4049/jimmunol.178.5.2901
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发表时间：
2007-03-01
影响因子：
4.4
通讯作者：
Tsubata, Takeshi
中科院分区：
文献类型：
--
作者：
Sato, Motohiko;Adachi, Takahiro;Tsubata, Takeshi
B细胞膜分子CD22和CD72在其胞浆部分含有ITIMs，并通过BCR负向调节信号。各种证据表明，由于缺乏CD22介导的信号调节，结扎含Ig G的BCR(Ig G-BCR)可传递增强的信号。然而，含有IgA和IgE的BCR的信号转导能力在很大程度上仍不清楚。在这项研究中，我们证明了与IgM-BCR相比，IgE-BCR和Ig G-BCR都传递增强信号，而不是Ig A-BCR。连接IgE-BCR不会诱导CD22介导的信号抑制所需的信号事件，而通过将CD22与BCR结合来恢复这些信号事件会取消信号增强。此外，IgE的细胞质部分足以抑制CD22介导的信号抑制，而IgA的细胞质部分则不足以抑制CD22介导的信号抑制。这些发现有力地表明，IgE的胞浆部分而不是IgA的胞浆部分逆转了CD22介导的信号抑制，导致通过IgE-BCR而不是IgA-BCR的信号增强。增强的IgE-BCR信号似乎在蠕虫感染过程中产生大量的IgE起作用，而通过IgA-BCR调节的信号可能对黏膜免疫所需的IgA的构成产生起关键作用。
The B cell membrane molecules CD22 and CD72 contain ITIMs in their cytoplasmic portion, and negatively regulate signaling through BCR. Various lines of evidence suggest that ligation of BCR containing IgG (IgG-BCR) transmits augmented signaling due to lack of CD22-mediated signal regulation. However, the signaling capacities of BCR containing IgA and IgE remain largely undefined. In this study, we demonstrate that both IgE-BCR and IgG-BCR, but not IgA-BCR, transmit augmented signaling compared with IgM-BCR. Ligation of IgE-BCR does not induce signaling events required for CD22-mediated signal inhibition, and restoration of these signaling events by coligation of CD22 with BCR abrogates signal augmentation. Furthermore, the cytoplasmic portion of IgE but not that of IgA is sufficient for suppressing CD22-mediated signal inhibition. These findings strongly suggest that the cytoplasmic portion of IgE but not that of IgA reverses CD22-mediated signal inhibition, leading to augmentation of signaling through IgE-BCR but not IgA-BCR. Augmented IgE-BCR signaling appears to play a role in production of large amounts of IgE during helminth infection, whereas regulated signaling through IgA-BCR may be crucial for constitutive production of IgA for mucosal immunity.