Liang Linda, Porter Evelyn M, Sha William C
Division of Immunology, Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
J Exp Med. 2002 Jul 1;196(1):97-108. doi: 10.1084/jem.20020298.
The recently described ligand-receptor pair, B7h-inducible costimulator (ICOS), is critical for germinal center formation and antibody responses. In contrast to the induced expression of the related costimulatory ligands B7.1 and B7.2, B7h is constitutively expressed on naive B cells and is surprisingly extinguished after antigen engagement and interleukin (IL)-4 cytokine signaling. Although signaling through both B cell receptor (BCR) and IL-4 receptor (R) converge on the extinction of B7h mRNA levels, BCR down-regulation occurs through Ca2+ mobilization, whereas IL-4R down-regulation occurs through a distinct Stat6-dependent pathway. During antigen-specific B cell activation, costimulation through CD40 signaling can reverse both BCR- and IL-4R-mediated B7h down-regulation. These data suggest that the CD40-CD40 ligand signaling pathway regulates B7h expression on activated B cells and may control whether antigen-activated B cells can express B7h and costimulate cognate antigen-activated T cells through ICOS.
最近描述的配体-受体对，即B7h诱导共刺激分子（ICOS），对生发中心形成和抗体反应至关重要。与相关共刺激配体B7.1和B7.2的诱导性表达不同，B7h在未活化B细胞上组成性表达，并且在抗原接触和白细胞介素（IL）-4细胞因子信号传导后令人惊讶地消失。尽管通过B细胞受体（BCR）和IL-4受体（R）的信号传导都导致B7h mRNA水平的消失，但BCR下调是通过Ca2+动员发生的，而IL-4R下调是通过一条独特的依赖Stat6的途径发生的。在抗原特异性B细胞活化过程中，通过CD40信号传导的共刺激可逆转BCR和IL-4R介导的B7h下调。这些数据表明，CD40-CD40配体信号传导途径调节活化B细胞上的B7h表达，并可能控制抗原活化的B细胞是否能够表达B7h并通过ICOS共刺激同源抗原活化的T细胞。
