Unexpected Help: Follicular Regulatory T Cells in the Germinal Center.

Unexpected Help: Follicular Regulatory T Cells in the Germinal Center.
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DOI:
10.3389/fimmu.2018.01536
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发表时间:
2018
影响因子:
7.3
通讯作者:
Dent AL
Dent AL
中科院分区:
医学2区
文献类型:
--
作者:
Xie MM;Dent AL

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滤泡辅助 T (Tfh) 细胞是生发中心 (GC) 形成所必需的,在 GC 内,为 B 细胞分化为浆母细胞和分泌高亲和力和同种型转换抗体 (Ab) 的浆细胞提供关键信号。 Foxp3+ T 细胞的一个特殊亚群,称为滤泡调节 T (Tfr) 细胞,也调节从 GC 中分泌抗体的细胞的分化。 Tfr 细胞在 GC 中的功能尚不清楚,然而,目前的主导范例是 Tfr 细胞抑制过度的 Tfh 和 GC B 细胞增殖,并有助于促进高亲和力 B 细胞的严格选择。 Foxp3+ T 细胞(Bcl6FC 小鼠)中 Bcl6 基因被专门删除的小鼠模型可以比其他方法更精确地研究 Tfr 细胞功能。该模型的研究表明,Tfr 细胞在维持 GC B 细胞增殖和 Ab 水平方面发挥着关键作用。 Tfr 细胞对 GC 产生这种积极“辅助”作用的部分机制是 Tfr 细胞衍生的 IL-10,它可以促进 B 细胞生长并进入 GC 暗区。最近对 Tfr 细胞的研究支持了 GC 反应中 Tfr 细胞功能的新范例。在这里,我们回顾了 Tfr 细胞功能的研究,并讨论了 Tfr 细胞在 GC 依赖性抗体反应中发挥主要辅助作用的证据。
Follicular helper T (Tfh) cells are necessary for germinal center (GC) formation and within the GC, provide key signals to B cells for their differentiation into plasmablasts and plasma cells that secrete high-affinity and isotype-switched antibody (Ab). A specialized subset of Foxp3+ T cells termed T follicular regulatory (Tfr) cells, also regulate the differentiation of Ab-secreting cells from the GC. Tfr-cell function in the GC is not well understood, however, the dominant paradigm currently is that Tfr cells repress excessive Tfh and GC B cell proliferation and help promote stringent selection of high-affinity B cells. A mouse model where the Bcl6 gene is specifically deleted in Foxp3+ T cells (Bcl6FC mice) allows the study of Tfr cell function with more precision than other approaches. Studies with this model have shown that Tfr cells play a key role in maintaining GC B cell proliferation and Ab levels. Part of the mechanism for this positive “helper” effect of Tfr cells on the GC is Tfr cell-derived IL-10, which can promote B cell growth and entry into the dark zone of the GC. Recent studies on Tfr cells support a new paradigm for Tfr cell function in the GC reaction. Here, we review studies on Tfr cell functions and discuss the evidence that Tfr cells can have a major helper role in the GC-dependent Ab response.
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