CEACAM1 is a potent regulator of B cell receptor complex-induced activation
CEACAM1 is a potent regulator of B cell receptor complex-induced activation
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DOI：
10.1189/jlb.1202594
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发表时间：
2003-07-01
影响因子：
5.5
通讯作者：
Singer, BB
中科院分区：
文献类型：
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作者：
Greicius, G;Severinson, E;Singer, BB
癌胚抗原相关细胞粘附分子1 （CEACAM1, CD66a）是免疫球蛋白（Ig）超家族的一员，以前被认为是上皮细胞、内皮细胞和造血细胞中的粘附和信号分子。在这里，我们发现CEACAM1亚型表达模式在未激活和激活的原代小鼠B淋巴细胞中是不同的，并且CEACAM1影响B细胞受体复合物介导的激活。当ceacam1特异性单克隆抗体与表面IgM交联结合时，强烈触发小鼠B细胞增殖。然而，单独添加抗ceacam1时不具有有丝分裂性。与其他B细胞激活剂（如存在白细胞介素-4或脂多糖的抗igm）相比，增殖更明显，持续时间更长。表达ceacam1的成纤维细胞也发挥了类似的共刺激作用，表明同源性CEACAM1-CEACAM1细胞介导的结合是ceacam1触发的B细胞信号传导的生理刺激。抗ceacam1 /抗igm活化细胞以淋巴细胞功能相关抗原1依赖性方式聚集。此外，被抗ceacam1 /抗igm激活的细胞分泌Ig，但不进行Ig类别转换。抗ceacam1诱导c-Jun n末端激酶（应激活化蛋白激酶）磷酸化，但不激活细胞外信号调节激酶或p38丝裂原活化蛋白激酶。
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is a member of the immunoglobulin (Ig) superfamily, previously characterized as an adhesion and signaling molecule in epithelial, endothelial, and hematopoietic cells. Here, we show that the CEACAM1 isoform expression pattern is different in nonactivated and activated primary mouse B lymphocytes and that CEACAM1 influences B cell receptor complex-mediated activation. A CEACAM1-specific monoclonal antibody strongly triggered proliferation of mouse B cells when combined with surface IgM cross-linking. However, anti-CEACAM1 was not mitogenic when added alone. The proliferation was more pronounced and lasted longer as compared with other activators of B cells, such as anti-IgM in the presence of interleukin-4 or lipopolysaccharide. A similar, costimulatory effect was exerted by CEACAM1-expressing fibroblasts, indicating that homophilic CEACAM1-CEACAM1 cell-mediated binding is the physiological stimulus for CEACAM1-triggered B cell signaling. The anti-CEACAM1/anti-IgM-activated cells aggregated in a lymphocyte function-associated antigen-1-dependent manner. Furthermore, cells that were activated by anti-CEACAM1/anti-IgM secreted Ig but did not go through Ig class-switching. Anti-CEACAM1 induced phosphorylation of c-Jun N-terminal kinase (stress-activated protein kinase) but did not activate the extracellular signal-regulated kinase or p38 mitogen-activated protein kinases.