Marshall L S, Shepherd D M, Ledbetter J A, Aruffo A, Noelle R J
Biochemistry Graduate Program, Dartmouth Medical School, Lebanon, NH 03756.
J Immunol. 1994 May 15;152(10):4816-25.
gp39 is expressed on anti-CD3-activated Th, and binds CD40 on the B cell, driving B cell cycle entry. In this study, the signal-transduction pathway initiated in B cells as a consequence of interacting with activated Th is examined. Unlike anti-membrane Ig (anti-mlg) or anti-MHC class II, plasma membranes (PM) isolated from anti-CD3-activated Th, PMAct did not trigger an increase in the B cell intracellular concentrations of cAMP or calcium. In addition, PMAct did not stimulate protein kinase C activation as measured by myristoylated alanine-rich C-kinase substrate (MARCKS) phosphorylation and protein kinase C translocation. The failure to detect these biochemical events may be caused by the asynchrony with which PMAct induce these normally transient biochemical changes. Alternatively, PMAct may not trigger these events. PMAct did induce the tyrosine phosphorylation of several B cell substrates. Neutralizing Abs directed against gp39 inhibited PMAct-induced protein tyrosine phosphorylation of B cell substrates. These results suggest that cognate interactions in B cells initiate a signal-transduction pathway that is different from the pathway initiated by cross-linking of mlg or MHC class II.
gp39在抗CD3激活的Th细胞上表达，并与B细胞上的CD40结合，驱动B细胞进入细胞周期。在本研究中，我们检测了B细胞因与激活的Th细胞相互作用而启动的信号转导途径。与抗膜Ig（抗mlg）或抗MHC II类分子不同，从抗CD3激活的Th细胞（PMAct）分离的质膜（PM）不会引发B细胞内cAMP或钙浓度的增加。此外，如通过富含肉豆蔻酰化丙氨酸的C激酶底物（MARCKS）磷酸化和蛋白激酶C易位所测定的，PMAct不会刺激蛋白激酶C的激活。未能检测到这些生化事件可能是由于PMAct诱导这些通常短暂的生化变化的不同步性所致。或者，PMAct可能不会引发这些事件。PMAct确实诱导了几种B细胞底物的酪氨酸磷酸化。针对gp39的中和抗体抑制了PMAct诱导的B细胞底物的蛋白酪氨酸磷酸化。这些结果表明，B细胞中的同源相互作用启动了一条与mlg或MHC II类分子交联所启动的途径不同的信号转导途径。
