Germinal center B cells constitute a predominant physiological source of IL-4: Implication for Th2 development in vivo
Germinal center B cells constitute a predominant physiological source of IL-4: Implication for Th2 development in vivo
复制标题
DOI：
10.4049/jimmunol.168.7.3165
复制
发表时间：
2002-04-01
影响因子：
4.4
通讯作者：
Borrebaeck, CAK
中科院分区：
文献类型：
--
作者：
Johansson-Lindbom, B;Borrebaeck, CAK
保护性免疫力取决于免疫系统适当调整对感染因子性质的反应的能力。CD 4 + Th细胞通过分泌极化模式的细胞因子参与这种协调。尽管动物模型和体外人类细胞中的Th 2发育在很大程度上取决于IL-4，但体内提供初始IL-4的细胞的性质仍然难以捉摸。在这份报告中，我们描述了解剖定位以及身份的IL-4产生细胞在人类扁桃体，一个代表性的次级淋巴器官。我们证明，IL-4的生产是一个正常的和内在的功能，生发中心（GC）B细胞。我们还发现IL-4的表达高度局限于GC，其中B细胞构成了主要的细胞来源。此外，结肠粘膜的免疫荧光分析显示，与扁桃体相比，IL-4表达细胞的模式惊人地相似，表明GC B细胞产生IL-4不是上呼吸道的独特特征。我们的研究结果表明，GC提供了最合适的微环境IL-4依赖性Th 2极化在体内，并暗示GC B细胞在这一分化过程中的关键作用。
Protective immunity depends upon the capability of the immune system to properly adapt the response to the nature of an infectious agent. CD4+ Th cells are implicated in this orchestration by secreting a polarized pattern of cytokines. Although Th2 development in animal models and in human cells in vitro to a large extent depends on IL-4, the nature of the cells that provide the initial IL-4 in vivo is still elusive. In this report, we describe the anatomical localization as well as the identity of IL-4-producing cells in human tonsil, a representative secondary lymphoid organ. We demonstrate that IL-4 production is a normal and intrinsic feature of germinal center (GC) B cells. We also show that expression of IL-4 is highly confined to the GCs, in which the B cells constitute the prevalent cellular source. Furthermore, immunofluorescence analysis of colon mucosa reveals a strikingly similar pattern of IL-4-expressing cells compared with tonsils, demonstrating that IL-4 production from GC B cells is not a unique feature of the upper respiratory tract. Our results show that GCs provide the most appropriate microenvironment for IL-4-dependent Th2 polarization in vivo and imply a critical role for GC B cells in this differentiation process.