Sen G, Bikah G, Venkataraman C, Bondada S
Department of Microbiology and Immunology, Sanders Brown Center on Aging, University of Kentucky, Lexington 40536-0230, USA.
Eur J Immunol. 1999 Oct;29(10):3319-28. doi: 10.1002/(SICI)1521-4141(199910)29:10<3319::AID-IMMU3319>3.0.CO;2-9.
CD5, a membrane-associated glycoprotein, has been shown to negatively regulate antigen receptor-mediated growth responses in peritoneal B lymphocytes, thymocytes and mature T cells. The CD5-expressing peritoneal B cells (B-1) that are normally unresponsive to B cell receptor (BCR)-mediated growth signals mount a proliferative response to BCR cross-linking if the CD5 gene is deleted or if the CD5 molecule is sequestered away from the BCR. SHP-1, a cytosolic protein tyrosine phosphatase, has also been implicated in the negative regulation of antigen receptor-mediated signaling. The present study shows that SHP-1 is constitutively associated with the BCR in B-1 cells. This association is mediated in part by CD5, as it is reduced substantially after antigen receptor ligation in CD5(-/-) B-1 cells, and upon sequestration of CD5 from the antigen receptor complexes in wild-type B-1 cells. Prior cross-linking of CD5 also restores a normal calcium mobilization response as well as NF-kappaB activation in B-1 cells. These data support a model whereby CD5 negatively regulates antigen receptor-mediated growth signals by recruiting SHP-1 into the BCR complex in B-1 cells.
CD5是一种膜相关糖蛋白，已被证明可负向调节腹膜B淋巴细胞、胸腺细胞和成熟T细胞中抗原受体介导的生长反应。正常情况下，对B细胞受体（BCR）介导的生长信号无反应的表达CD5的腹膜B细胞（B-1细胞），如果CD5基因被删除或者CD5分子与BCR分离，则会对BCR交联产生增殖反应。SHP-1是一种胞质蛋白酪氨酸磷酸酶，也参与了抗原受体介导信号的负向调节。本研究表明，SHP-1在B-1细胞中与BCR组成性结合。这种结合部分由CD5介导，因为在CD5（-/-）B-1细胞中抗原受体连接后，以及在野生型B-1细胞中CD5从抗原受体复合物中分离后，这种结合会显著减少。预先交联CD5还可恢复B-1细胞中正常的钙动员反应以及NF-κB激活。这些数据支持了一个模型，即CD5通过将SHP-1招募到B-1细胞的BCR复合物中，负向调节抗原受体介导的生长信号。
