Generation of T follicular helper cells in vitro: requirement for B-cell receptor cross-linking and cognate B- and T-cell interaction.

Generation of T follicular helper cells in vitro: requirement for B-cell receptor cross-linking and cognate B- and T-cell interaction.
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DOI:
10.1111/imm.12834
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发表时间:
2018-03
期刊:
影响因子:
6.4
通讯作者:
Temchura V
Temchura V
中科院分区:
医学2区
文献类型:
--
作者:
Kolenbrander A;Grewe B;Nemazee D;Überla K;Temchura V

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天然CD 4 + T细胞分化为T滤泡辅助细胞(Tfh)的体外模型的最低要求仍在研究中。我们在含有匹配的B细胞和T细胞表位的HIV衍生病毒样颗粒存在下,将来自幼稚小鼠的野生型和T细胞受体(TCR)转基因CD 4 + T细胞与树突状细胞和B细胞受体(BCR)转基因B细胞共培养。这种共培养诱导了高达10%的野生型和高达40%的TCR转基因CD 4 + T细胞中Tfh主调节转录因子BCL-6和CXCR 5的共表达。表型标志物、白细胞介素-21的产生和B细胞向IgG 1的同种型转换进一步表明体外诱导的Tfh细胞的辅助功能。树突状细胞支持功能性Tfh细胞的产生,但在没有同源B细胞的情况下不能诱导它们。因此,我们的研究提供了一个强大的实验系统,用于体外有效生成功能活性Tfh细胞,并证实了同源B-和T-细胞串扰对Tfh分化过程的重要性。
The minimum requirements for in vitro modelling of natural CD4+ T‐cell differentiation into T follicular helper (Tfh) cells are still under investigation. We co‐cultured wild‐type and T‐cell receptor (TCR) transgenic CD4+ T cells from naive mice with dendritic cells and B‐cell receptor (BCR) transgenic B cells in the presence of HIV‐derived virus‐like particles containing matched B‐cell and T‐cell epitopes. This co‐culturing induced co‐expression of Tfh‐master regulator transcription factor BCL‐6 and CXCR5 in up to 10% of the wild‐type and up to 40% of the TCR‐transgenic CD4+ T cells. Phenotypic markers, production of interleukin‐21 and isotype switching of the B cells to IgG1 further indicated a helper function of the induced Tfh cells in vitro. Dendritic cells supported the generation of functional Tfh cells, but were unable to induce them without cognate B cells. Hence, our study presents a robust experimental system for efficient generation of functionally active Tfh cells in vitro and confirms the importance of cognate B‐ and T‐cell cross‐talk for the Tfh differentiation process.
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