Dong C, Temann U A, Flavell R A
Section of Immunobiology, Yale University School of Medicine and Howard Hughes Medical Institute, New Haven, CT 06514, USA.
J Immunol. 2001 Mar 15;166(6):3659-62. doi: 10.4049/jimmunol.166.6.3659.
Inducible costimulator (ICOS) is a new member of the CD28/CTLA-4 family that is expressed on activated and germinal center (GC) T cells. Recently, we reported that ICOS-deficient mice exhibited profound defects in T cell activation and effector function. Ab responses in a T-dependent primary reaction and in a murine asthma model were also diminished. In the current study, we investigate the mechanism by which ICOS regulates humoral immunity and examine B cell GC reactions in the absence of ICOS. We found that ICOS(-/-) mice, when immunized with SRBC, had smaller GCs. Furthermore, IgG1 class switching in the GCs was impaired. Remarkably, GC formation in response to a secondary recall challenge was completely absent in ICOS knockout mice. These data establish a critical role of ICOS in regulation of humoral immunity.
诱导性共刺激分子（ICOS）是CD28/CTLA-4家族的新成员，在活化的生发中心（GC）T细胞上表达。最近，我们报道ICOS缺陷小鼠在T细胞活化和效应功能方面表现出严重缺陷。T细胞依赖性初次反应和小鼠哮喘模型中的抗体反应也减弱。在本研究中，我们研究了ICOS调节体液免疫的机制，并在缺乏ICOS的情况下检查B细胞GC反应。我们发现，用绵羊红细胞免疫时，ICOS（-/-）小鼠的生发中心较小。此外，生发中心的IgG1类别转换受损。值得注意的是，ICOS基因敲除小鼠对二次回忆攻击的生发中心形成完全缺失。这些数据确立了ICOS在体液免疫调节中的关键作用。
