CEACAM1 is a negative coreceptor for the B cell receptor and promotes CD19-mediated adhesion of B cells in a PI3K-dependent manner
CEACAM1 is a negative coreceptor for the B cell receptor and promotes CD19-mediated adhesion of B cells in a PI3K-dependent manner
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DOI：
10.1189/jlb.0109037
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发表时间：
2009-08-01
影响因子：
5.5
通讯作者：
Shively, John E.
中科院分区：
文献类型：
--
作者：
Lobo, Elizabeth O.;Zhang, Zhifang;Shively, John E.
在抗原结合后，BCR转导一个信号，最终导致B细胞的增殖或AICD。辅助受体的参与和随后BCR信号通路的修饰是引导B细胞走向其适当命运的机制。例如，在没有共受体参与的情况下，抗sigm抗体可诱导人Daudi B细胞淋巴瘤细胞系的凋亡。携带itim的B细胞辅助受体可能作为负性辅助受体，包括FcR γ IIb、CD22、CD72和CEACAM1 （CD66a）。虽然CEACAM1在T细胞中作为抑制性辅助受体的作用已被确立，但其在B细胞中的作用尚不明确。我们发现，与WT Daudi细胞相比，CEACAM1敲除克隆中抗sigm抗体和PI3K抑制剂ly294002诱导的细胞凋亡显著减少，抗sigm处理诱导WT细胞中CEACAM1酪氨酸磷酸化和与SHP-1的关联。相比之下，用抗cd19抗体处理WT Daudi细胞不会诱导细胞凋亡，并减少酪氨酸磷酸化和SHP-1对CEACAM1的募集。因此，与其在T细胞中的功能相似，CEACAM1可能作为抑制性B细胞辅助受体，最有可能通过募集SHP-1和抑制pi3k促进的激活途径。抗sigm或抗cd19抗体激活B细胞也导致CEACAM1促进细胞聚集，也是以pi3k依赖的方式。j . Leukoc。生物学报。86:205-218；2009.
Upon antigen binding, the BCR transduces a signal culminating in proliferation or in AICD of the B cell. Coreceptor engagement and subsequent modification of the BCR signal pathway are mechanisms that guide the B cell to its appropriate fate. For example, in the absence of coreceptor engagement, anti-sIgM antibodies induce apoptosis in the human Daudi B cell lymphoma cell line. ITIM-bearing B cell coreceptors that potentially may act as negative coreceptors include FcR gamma IIb, CD22, CD72, and CEACAM1 (CD66a). Although the role of CEACAM1 as an inhibitory coreceptor in T cells has been established, its role in B cells is poorly defined. We show that anti-sIgM antibody and PI3K inhibitor LY294002-induced apoptosis are reduced significantly in CEACAM1 knock-down clones compared with WT Daudi cells and that anti-sIgM treatment induced CEACAM1 tyrosine phosphorylation and association with SHP-1 in WT cells. In contrast, treatment of WT Daudi cells with anti-CD19 antibodies does not induce apoptosis and has reduced tyrosine phosphorylation and SHP-1 recruitment to CEACAM1. Thus, similar to its function in T cells, CEACAM1 may act as an inhibitory B cell coreceptor, most likely through recruitment of SHP-1 and inhibition of a PI3K-promoted activation pathway. Activation of B cells by anti-sIgM or anti-CD19 antibodies also leads to cell aggregation that is promoted by CEACAM1, also in a PI3K-dependent manner. J. Leukoc. Biol. 86: 205-218; 2009.