Lenschow D J, Sperling A I, Cooke M P, Freeman G, Rhee L, Decker D C, Gray G, Nadler L M, Goodnow C C, Bluestone J A
Committee on Immunology, University of Chicago, IL 60637.
J Immunol. 1994 Sep 1;153(5):1990-7.
Ag-pulsed B cells are potent APCs, in part, because of the ability of the Ig receptor to mediate rapid and specific Ag uptake. However, it is also known that full T cell activation requires signals delivered by costimulatory molecules, which naive B cells seem to lack. This study examines the effect Ig receptor engagement has on the expression and function of a new CD28 counter-receptor, B7-2. Unlike B7-1 (B7), B7-2 was rapidly induced on the cell surface of B cells after engagement of the Ig receptor by either anti-Ig mAbs or hen egg lysozyme (HEL) on normal and HEL-specific B cell receptor transgenic B cells, respectively. Furthermore, B7-2 expression was up-regulated on tolerant B cells isolated from HEL/anti-HEL double transgenic mice after Ag stimulation, although at lower levels than on nontolerant transgenic B cells. No significant cell surface levels of B7-1(B7) were observed under these conditions. Finally, the B7-2 molecules induced by Ig cross-linking costimulated T cell proliferation in a CD28-dependent manner, independent of B7-1(B7) expression. Thus, the effectiveness of Ag-specific B cells as APCs depends on both their enhanced Ag uptake, mediated by the B cell receptor, and immediate up-regulation of a potent costimulatory molecule, B7-2.
抗原刺激的B细胞是有效的抗原呈递细胞(APC),部分原因是免疫球蛋白(Ig)受体能够介导快速且特异性的抗原摄取。然而,众所周知,T细胞的完全激活需要共刺激分子传递信号,而初始B细胞似乎缺乏这些信号。本研究探讨了Ig受体结合对一种新的CD28反受体B7-2的表达和功能的影响。与B7-1(B7)不同,在正常B细胞和HEL特异性B细胞受体转基因B细胞中,分别用抗Ig单克隆抗体或溶菌酶(HEL)刺激Ig受体后,B7-2会迅速在B细胞表面被诱导表达。此外,从HEL/抗HEL双转基因小鼠分离的耐受B细胞在抗原刺激后,B7-2表达上调,尽管其水平低于非耐受转基因B细胞。在这些条件下未观察到B7-1(B7)的显著细胞表面水平。最后,由Ig交联诱导的B7-2分子以CD28依赖的方式共刺激T细胞增殖,与B7-1(B7)的表达无关。因此,抗原特异性B细胞作为APC的有效性取决于其通过B细胞受体介导的增强的抗原摄取以及强效共刺激分子B7-2的即时上调。