Toll-like receptor expression and responsiveness of distinct murine splenic and mucosal B-cell subsets.
Toll-like receptor expression and responsiveness of distinct murine splenic and mucosal B-cell subsets.
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Toll样受体表达以及不同鼠脾和粘膜B细胞亚群的反应性。
DOI：
10.1371/journal.pone.0000863
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发表时间：
2007-09-12
期刊：
影响因子：
3.7
通讯作者：
Pulendran, Bali
中科院分区：
文献类型：
--
作者：
Gururajan, Murali;Jacob, Joshy;Pulendran, Bali
Toll 样受体 (TLR) 是模式识别受体，可识别病原体相关分子模式并触发先天免疫，从而启动适应性免疫。 TLR 介导的树突状细胞 (DC) 激活已知是细胞和体液免疫反应启动的关键事件。然而，最近的研究表明 B 细胞也表达 TLR，并且它们可以通过 TLR 配体激活。然而，这种 B 细胞激活是否只发生在记忆 B 细胞上，或者是否也可以发生在真正的幼稚 B 细胞上，仍然存在争议。此外，TLR 在不同 B 细胞亚群上的表达和功能相关性尚不清楚，已知这些 B 细胞亚群在体液反应中发挥不同的作用。在这项研究中，我们研究了不同 TLR 在不同的小鼠 B 细胞亚群（幼稚细胞、记忆细胞、滤泡细胞、边缘区细胞、B-1 细胞和集合淋巴结）中的表达模式。与报道的人外周血幼稚 B 细胞中 TLR 的限制性表达模式相反，鼠脾幼稚 B 细胞表达除 TLR5 和 8 之外的多种 TLR。与这种相对广泛的表达模式一致，在没有 B 细胞受体交联的情况下，鼠幼稚 B 细胞在体外增殖并分泌针对多种 TLR 激动剂的抗体。此外，我们还观察到滤泡、边缘区、B-1 和派尔氏集结 B 细胞亚群的抗体分泌模式存在细微差异。因此，各种 B 细胞亚群，包括真正的幼稚 B 细胞，表达多个 TLR，并且即使在没有树突状细胞激活或 T 细胞帮助的情况下，通过此类 TLR 发出的信号也会导致其强劲的增殖和抗体分泌。
Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen associated molecular patterns and trigger innate immunity leading to initiation of adaptive immunity. TLR-mediated activation of dendritic cells (DCs) is known to be a critical event in the initiation of cellular and humoral immune responses. Recent work however suggests that B cells also express TLRs, and that they can be activated via TLR ligands. However, whether such B cell activation occurs only on memory B cells, or whether it can also occur on truly naïve B cells remains controversial. Furthermore, the expression and functional relevance of TLRs on distinct subsets of B cells, which are known to play differential roles in humoral responses is not known. In this study, we investigated the expression pattern of different TLRs in distinct subsets of murine B cells (naïve, memory, follicular, marginal zone, B-1 and peyer's patch). In contrast to the reported restricted expression pattern of TLRs in human peripheral blood naïve B cells, murine splenic naïve B cells express a variety of TLRs with the exception of TLR5 and 8. Consistent with this relatively broad expression pattern, murine naive B cells proliferate and secrete antibody to a variety of TLR agonists in vitro, in the absence of B-cell receptor cross-linking. In addition, we observed subtle differences in the antibody secretion pattern of follicular, marginal zone, B-1 and peyer's patch B-cell subsets. Thus various B cell subsets, including truly naïve B cells, express multiple TLRs, and signaling via such TLRs results in their robust proliferation and antibody secretion, even in the absence of dendritic cell activation, or T-cell help.
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