Cytokine-Mediated Regulation of Plasma Cell Generation: IL-21 Takes Center Stage.
Cytokine-Mediated Regulation of Plasma Cell Generation: IL-21 Takes Center Stage.
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DOI：
10.3389/fimmu.2014.00065
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发表时间：
2014
影响因子：
7.3
通讯作者：
Tangye SG
中科院分区：
文献类型：
--
作者：
Moens L;Tangye SG
在我们的生活中，我们被各种入侵病原体的持续威胁所包围。我们的免疫系统已经进化出多种机制来有效地应对这些威胁，以防止它们引起疾病。成熟B细胞终末分化为浆细胞（PC）-免疫系统的抗体（Ab）分泌细胞-对于产生保护性和长寿命的体液免疫应答至关重要。事实上，通过活化的B细胞有效产生抗原（Ag）特异性Ab是大多数目前可用疫苗成功的基础。成熟B细胞库由几个亚群组成，根据大小、表面标志物表达、位置和Ag暴露来区分，并且它们都具有分化成PC的能力。为了使B细胞获得产生抗体的能力，它必须经历由基因表达变化驱动的广泛分化过程。存在引起B细胞活化和分化的两大类Ag：T细胞依赖性（TD）或T细胞非依赖性（TI）。除了B细胞亚群和抗原的性质之外，重要的是要考虑也可以影响B细胞分化如何实现的细胞因子环境。因此，虽然许多细胞因子在体外用模拟TD和TI刺激物活化后可诱导B细胞的Ab分泌，但它们可具有不同的功效和特异性，并且通常可优先诱导一种特定IG同种型的产生而不是另一种。在这里，我们将提供一个概述在体外研究（小鼠和人类起源），评估不同的细胞因子在诱导分化的不同B细胞亚群的PC谱系的作用。我们将特别强调IL-21，它已成为人类终末B细胞分化的最有效诱导剂。我们还将重点关注IL-21的作用和B细胞功能缺陷，以及这些缺陷如何导致人类免疫病理学，如原发性免疫缺陷和B细胞介导的自身免疫性疾病。
During our life, we are surrounded by continuous threats from a diverse range of invading pathogens. Our immune system has evolved multiple mechanisms to efficiently deal with these threats so as to prevent them from causing disease. Terminal differentiation of mature B cells into plasma cells (PC) – the antibody (Ab) secreting cells of the immune system – is critical for the generation of protective and long-lived humoral immune responses. Indeed, efficient production of antigen (Ag)-specific Ab by activated B cells underlies the success of most currently available vaccines. The mature B-cell pool is composed of several subsets, distinguished from one according to size, surface marker expression, location, and Ag exposure, and they all have the capacity to differentiate into PCs. For a B-cell to acquire the capacity to produce Abs, it must undergo an extensive differentiation process driven by changes in gene expression. Two broad categories of Ags exist that cause B-cell activation and differentiation: T cell dependent (TD) or T cell independent (TI). In addition to the B-cell subset and nature of the Ag, it is important to consider the cytokine environment that can also influence how B-cell differentiation is achieved. Thus, while many cytokines can induce Ab-secretion by B cells after activation with mimics of TD and TI stimuli in vitro, they can have different efficacies and specificities, and can often preferentially induce production of one particular Ig isotype over another. Here, we will provide an overview of in vitro studies (mouse and human origin) that evaluated the role of different cytokines in inducing the differentiation of distinct B-cell subsets to the PC lineage. We will place particular emphasis on IL-21, which has emerged as the most potent inducer of terminal B-cell differentiation in humans. We will also focus on the role of IL-21 and defects in B-cell function and how these contribute to human immunopathologies such as primary immunodeficiencies and B-cell mediated autoimmune conditions.