Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals
Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals
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DOI：
10.4049/jimmunol.171.4.1684
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发表时间：
2003-08-15
影响因子：
4.4
通讯作者：
Manz, RA
中科院分区：
文献类型：
--
作者：
Cassese, G;Arce, S;Manz, RA
最近的结果表明，浆细胞的寿命不是一种内在能力，而是取决于其环境中产生的未知因素。在这项研究中，我们表明，细胞因子IL-5，IL-6，TNF-α，和基质细胞衍生因子-Ia以及通过CD 44的信号支持分离的骨髓浆细胞的存活。对于早期B细胞发育至关重要的细胞因子IL-7和干细胞因子不介导浆细胞存活，表明浆细胞和早期B细胞具有不同的存活要求。如在IL-6缺陷小鼠中所示，IL-6是正常诱导所需的，但不是维持体内浆细胞应答所需的，表明个体存活因子的作用是多余的。分离的浆细胞的最佳存活需要通过协同作用的因素的组合的刺激。这些结果有力地支持了浆细胞存活依赖于小生境的概念，在小生境中，特异性信号的组合，包括IL-5、IL-6、基质细胞衍生因子-1 α、TNF-α和CD 44配体，提供了介导浆细胞寿命所需的环境。
Recent results suggest that plasma cell longevity is not an intrinsic capacity, but depends on yet unknown factors produced in their environment. In this study, we show that the cytokines IL-5, IL-6, TNF-alpha, and stromal cell-derived factor-la as well as signaling via CD44 support the survival of isolated bone marrow plasma cells. The cytokines IL-7 and stem cell factor, crucially important for early B cell development, do not mediate plasma cell survival, indicating that plasma cells and early B cells have different survival requirements. As shown in IL-6-deficient mice, IL-6 is required for a normal induction, but not for the maintenance of plasma cell responses in vivo, indicating that the effects of individual survival factors are redundant. Optimal survival of isolated plasma cells requires stimulation by a combination of factors acting synergistically. These results strongly support the concept that plasma cell survival depends on niches in which a combination of specific signals, including IL-5, IL-6, stromal cell-derived factor-1alpha, TNF-alpha, and ligands for CD44, provides an environment required to mediate plasma cell longevity.