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A novel recycling mechanism of native IgE-antigen complexes in human B cells facilitates transfer of antigen to dendritic cells for antigen presentation
Journal of Allergy and Clinical Immunology ( IF 14.2 ) Pub Date : 2017-10-23 , DOI: 10.1016/j.jaci.2017.09.024
Paul Engeroff , Marc Fellmann , Daniel Yerly , Martin F. Bachmann , Monique Vogel

Background

IgE-immune complexes (IgE-ICs) have been shown to enhance antibody and T-cell responses in mice by targeting CD23 (FcεRII), the low-affinity receptor for IgE on B cells. In humans, the mechanism by which CD23-expressing cells take up IgE-ICs and process them is not well understood.

Objective

To investigate this question, we compared the fate of IgE-ICs in human B cells and in CD23-expressing monocyte-derived dendritic cells (moDCs) that represent classical antigen-presenting cells and we aimed at studying IgE-dependent antigen presentation in both cell types.

Methods

B cells and monocytes were isolated from peripheral blood, and monocytes were differentiated into moDCs. Both cell types were stimulated with IgE-ICs consisting of 4-hydroxy-3-iodo-5-nitrophenylacetyl (NIP)–specific IgE JW8 and NIP-BSA to assess binding, uptake, and degradation dynamics. To assess CD23-dependent T-cell proliferation, B cells and moDCs were pulsed with IgE-NIP-tetanus toxoid complexes and cocultured with autologous T cells.

Results

IgE-IC binding was CD23-dependent in B cells, and moDCs and CD23 aggregation, as well as IgE-IC internalization, occurred in both cell types. Although IgE-ICs were degraded in moDCs, B cells did not degrade the complexes but recycled them in native form to the cell surface, enabling IgE-IC uptake by moDCs in cocultures. The resulting proliferation of specific T cells was dependent on cell-cell contact between B cells and moDCs, which was explained by increased upregulation of costimulatory molecules CD86 and MHC class II on moDCs induced by B cells.

Conclusions

Our findings argue for a novel model in which human B cells promote specific T-cell proliferation on IgE-IC encounter. On one hand, B cells act as carriers transferring antigen to more efficient antigen-presenting cells such as DCs. On the other hand, B cells can directly promote DC maturation and thereby enhance T-cell stimulation.



中文翻译:

人B细胞中天然IgE抗原复合物的新型回收机制有助于将抗原转移至树突状细胞以进行抗原呈递

背景

IgE免疫复合物(IgE-ICs)已显示可通过靶向CD23(FcεRII)(一种B细胞上IgE的低亲和力受体)来增强小鼠的抗体和T细胞反应。在人类中,表达CD23的细胞吸收IgE-IC并处理它们的机制尚不十分清楚。

客观的

为了研究这个问题,我们比较了人类B细胞和代表经典抗原呈递细胞的表达CD23的单核细胞衍生树突状细胞(moDC)中IgE-IC的命运,并且我们旨在研究两种细胞中IgE依赖性抗原呈递类型。

方法

从外周血中分离出B细胞和单核细胞,并将单核细胞分化为moDC。两种细胞类型均由包含4-羟基-3-碘-5-硝基苯基乙酰基(NIP)的IgE JW8和NIP-BSA组成的IgE-IC刺激,以评估结合,摄取和降解动力学。为了评估CD23依赖的T细胞增殖,用IgE-NIP-破伤风类毒素复合物对B细胞和moDC进行脉冲处理,并与自体T细胞共培养。

结果

IgE-IC结合在B细胞中是CD23依赖性的,在两种细胞类型中均发生了moDCs和CD23聚集以及IgE-IC内在化。尽管IgE-ICs在moDCs中降解,但B细胞不会降解复合物,而是将它们以天然形式再循环到细胞表面,从而使moDCs在共培养物中能够吸收IgE-IC。特异性T细胞的增殖取决于B细胞与moDC之间的细胞接触,这可以通过B细胞诱导的moDC上共刺激分子CD86和II类MHC上调的增加来解释。

结论

我们的发现证明了一种新颖的模型,其中人B细胞在IgE-IC遭遇时促进特定的T细胞增殖。一方面,B细胞充当将抗原转移到更有效的抗原呈递细胞(例如DC)的载体。另一方面,B细胞可直接促进DC成熟,从而增强T细胞刺激。

更新日期:2017-10-23
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