Identification of a new stromal cell type involved in the regulation of inflamed B cell follicles.
Identification of a new stromal cell type involved in the regulation of inflamed B cell follicles.
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DOI：
10.1371/journal.pbio.1001672
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发表时间：
2013-10
期刊：
影响因子：
9.8
通讯作者：
Bajénoff M
中科院分区：
文献类型：
--
作者：
Mionnet C;Mondor I;Jorquera A;Loosveld M;Maurizio J;Arcangeli ML;Ruddle NH;Nowak J;Aurrand-Lions M;Luche H;Bajénoff M
小鼠淋巴结中一种新的基质细胞类型的鉴定，这种细胞类型可以被B细胞激活，以划定炎症期间B细胞区的短暂边界淋巴结（LN）基质细胞为淋巴细胞提供生存信号和粘附基质。在免疫反应期间，B细胞滤泡扩大，质疑LN基质细胞如何管理这些细胞需求。在此，我们使用鼠命运映射系统来描述一种新的基质细胞类型，其位于静息LN的T细胞区。我们证明，在炎症时，B细胞滤泡逐渐侵入邻近的T细胞区，包围这些基质细胞并将其转化为CXCL 13分泌细胞，这些细胞反过来划定了生长滤泡的新边界。急性炎症淋巴结B细胞消融可消除这些细胞中的CXCL 13分泌，而B细胞中的LT-β缺陷会显著影响这种转化。总而言之，我们揭示了一个休眠的基质细胞亚群的存在，它可以被B细胞在功能上唤醒，以描绘炎症时它们扩张领土的短暂边界。免疫应答在淋巴器官如扁桃体和淋巴结（LN）中发展，其由白细胞（95%）和结构基质细胞（5%）组成。参与建立免疫应答的LN招募大量淋巴细胞并支持识别外源抗原的淋巴细胞的分裂，这提出了LN基质细胞如何管理这种巨大重塑的问题。在这项研究中，我们专注于淋巴结内称为生发中心的特定区域，这些区域包含B淋巴细胞的致密聚集体或滤泡，并研究了淋巴基质细胞如何促进初级B细胞滤泡重组为大的反应性次级滤泡。使用小鼠的命运映射系统，我们确定了一种新的基质细胞类型，驻留在非炎症静息淋巴结的T细胞区。我们证明，在炎症时，B细胞通常包含在B细胞滤泡内，逐渐侵入相邻的T细胞区，包围并将驻留的基质细胞转化为可以分泌CXCL 13（一种B细胞趋化因子）的细胞。这些CXCL 13分泌细胞反过来又起作用，描绘生长卵泡的新的瞬时边界。这种独特的多功能基质细胞类型的鉴定增加了我们对淋巴器官功能区隔化机制的理解。
Identification of a new stromal cell type in mouse lymph nodes that can be activated by B cells to delineate the transient boundaries of B cell zones during inflammation Lymph node (LN) stromal cells provide survival signals and adhesive substrata to lymphocytes. During an immune response, B cell follicles enlarge, questioning how LN stromal cells manage these cellular demands. Herein, we used a murine fate mapping system to describe a new stromal cell type that resides in the T cell zone of resting LNs. We demonstrated that upon inflammation, B cell follicles progressively trespassed into the adjacent T cell zone and surrounded and converted these stromal cells into CXCL13 secreting cells that in return delineated the new boundaries of the growing follicle. Acute B cell ablation in inflamed LNs abolished CXCL13 secretion in these cells, while LT-β deficiency in B cells drastically affected this conversion. Altogether, we reveal the existence of a dormant stromal cell subset that can be functionally awakened by B cells to delineate the transient boundaries of their expanding territories upon inflammation. Immune responses develop in lymphoid organs such as the tonsils and lymph nodes (LNs), which are composed of leukocytes (95%) and architectural stromal cells (5%). LNs involved in mounting an immune response recruit large numbers of lymphocytes and support the division of those that recognise the foreign antigen, raising the question of how LN stromal cells manage this tremendous remodeling. In this study, we focused on specific zones within the lymph node called germinal centres that comprise dense aggregates or follicles of B lymphocytes, and investigated how lymphoid stromal cells contribute to the reorganization of primary B cell follicles into large reactive secondary follicles. Using a fate mapping system in mice, we identified a new stromal cell type that resides in the T cell zone of noninflamed resting LNs. We demonstrate that upon inflammation, B cells usually contained within B cell follicles progressively trespass into the adjacent T cell zone and surround and convert resident stromal cells into cells that can secrete CXCL13, a B cell chemokine. These CXCL13-secreting cells in turn act to delineate the new transient boundaries of the growing follicle. Identification of this distinct versatile stromal cell type adds to our understanding of mechanisms underlying compartmentalization of lymphoid organs into their functional zones.
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