Langerhans cells promote early germinal center formation in response to Leishmania‐derived cutaneous antigens
Langerhans cells promote early germinal center formation in response to Leishmania‐derived cutaneous antigens
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朗格汉斯细胞响应利什曼原虫衍生的皮肤抗原促进早期生发中心形成
DOI：
10.1002/eji.201344263
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发表时间：
2014
影响因子：
5.4
通讯作者：
Ritter U
中科院分区：
文献类型：
--
作者：
Zimara N;Florian C;Schmid M;Malissen B;Kissenpfennig A;Männel DN;Edinger M;Hutchinson JA;Hoffmann P;Ritter U
早期GCs的有效形成依赖于GC B细胞和抗原免疫的CD4+滤泡辅助T细胞(TFH)之间的密切相互作用。细胞因子驱动的免疫球蛋白类转换和GC B细胞的体细胞超突变需要紧密稳定的TFH/B细胞结合物的形成。最近的研究表明，在感染主要利什曼原虫后，TFH/B细胞结合物的形成对B细胞的分化和分类转换是至关重要的。然而，负责TFH细胞启动真皮抗原的树突状细胞亚型目前尚不清楚。利用体内设计用于触发Langerin+DC亚群消融的转基因C57BL/6小鼠模型，我们证明了朗格汉斯细胞(LCS)耗尽后TFH/B细胞结合物的功能受到干扰：LC耗竭小鼠表现出从TFH/B细胞结合物分离的B细胞的体细胞超突变减少，并显著减少皮肤引流淋巴结内的GC反应。总之，这项研究揭示了LCS在皮肤感染主要利什曼原虫后促进GC B细胞分化方面不可或缺的作用。我们认为LCS是GC形成的关键调节因子，因此对过敏和自身免疫的发展以及未来的疫苗接种策略具有更广泛的影响。
Efficient formation of early GCs depends on the close interaction between GC B cells and antigen‐primed CD4+follicular helper T cells (TFH). A tight and stable formation of TFH/B cell conjugates is required for cytokine‐driven immunoglobulin class switching and somatic hypermutation of GC B cells. Recently, it has been shown that the formation of TFH/B cell conjugates is crucial for B‐cell differentiation and class switch following infection withLeishmania majorparasites. However, the subtype of DCs responsible for TFH‐cell priming against dermal antigens is thus far unknown. Utilizing a transgenic C57BL/6 mouse model designed to trigger the ablation of Langerin+DC subsets in vivo, we show that the functionality of TFH/B cell conjugates is disturbed after depletion of Langerhans cells (LCs): LC‐depleted mice show a reduction in somatic hypermutation in B cells isolated from TFH/B cell conjugates and markedly reduced GC reactions within skin‐draining lymph nodes. In conclusion, this study reveals an indispensable role for LCs in promoting GC B‐cell differentiation following cutaneous infection withLeishmania majorparasites. We propose that LCs are key regulators of GC formation and therefore have broader implications for the development of allergies and autoimmunity as well as for future vaccination strategies.