Pérez-Melgosa M, Hollenbaugh D, Wilson C B
Department of Immunology, University of Washington, Seattle 98195, USA.
J Immunol. 1999 Aug 1;163(3):1123-7.
CD40 ligand (CD40L) plays a crucial role in T cell-dependent B cell responses, but whether its abundance is a limiting factor in their development is unclear. This question was addressed in transgenic mice expressing the murine CD40L gene under the control of the IL-2-promoter (CD40Ltg+). The fraction of activated T cells from the CD40Ltg+ mice with detectable levels of surface CD40L was modestly greater (1.1- to 2-fold) than littermate controls and paralleled an approximately 1.8-fold increase in CD40L mRNA abundance. In response to trinitrophenol (TNP)-keyhole limpet hemocyanin and tetanus/diphtheria vaccine, CD40Ltg+ mice developed higher titers of high-affinity IgG and IgG1 Ab than wild-type mice. In contrast, the Ab response of CD40Ltg+ and control mice was similar in response to the T-independent Ag TNP-Ficoll. These results suggest that a modest increment in expression of CD40L accelerates the development of T-dependent responses, and that CD40L plays a limiting role in the induction of high-affinity Ab and Ab-class switching.
CD40配体（CD40L）在T细胞依赖性B细胞反应中起关键作用，但其丰度是否是这些反应发展中的限制因素尚不清楚。在白细胞介素-2启动子（CD40Ltg+）控制下表达鼠CD40L基因的转基因小鼠中研究了这个问题。来自CD40Ltg+小鼠且表面CD40L水平可检测的活化T细胞比例比同窝对照适度更高（1.1至2倍），并且与CD40L mRNA丰度增加约1.8倍相平行。针对三硝基苯酚（TNP）-钥孔戚血蓝蛋白和破伤风/白喉疫苗，CD40Ltg+小鼠产生的高亲和力IgG和IgG1抗体滴度高于野生型小鼠。相比之下，CD40Ltg+小鼠和对照小鼠对非T细胞依赖性抗原TNP-菲可的抗体反应相似。这些结果表明，CD40L表达的适度增加加速了T细胞依赖性反应的发展，并且CD40L在高亲和力抗体的诱导和抗体类别转换中起限制作用。
