Cytokine-secreting follicular T cells shape the antibody repertoire.

Cytokine-secreting follicular T cells shape the antibody repertoire.
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DOI:
10.1038/ni.1715
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发表时间:
2009-04
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
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高亲和力抗体对宿主保护至关重要,也是成功疫苗的基础。此类抗体的产生需要T细胞依赖性辅助,这种辅助介导生发中心(GC)反应,其中B细胞发生突变和选择。利用白细胞介素4(IL - 4)报告系统,我们发现滤泡辅助性CD4 + T(TFH)细胞基本上包含了淋巴结中所有分泌细胞因子的T细胞,并且在功能上不同于在外周组织中分泌相同细胞因子的T细胞。具有不同细胞因子谱的TFH细胞可作为与B细胞的结合物被分离出来,这些B细胞正在进行细胞因子特异性免疫球蛋白类别转换,并伴有体细胞高频突变的迹象。这些发现支持一种模型,即B细胞竞争TFH细胞产生的细胞因子,这些细胞因子塑造抗体反应的亲和力和同种型。
High-affinity antibodies are critical for host protection and underlie successful vaccines. Generation of such antibodies requires T cell-dependent help, which mediates germinal center (GC) reactions where mutation and selection of B cells occurs. Using an interleukin 4 (IL-4)-reporter system, we show that follicular CD4+ T (TFH) cells comprised essentially all of the cytokine-secreting T cells in lymph nodes and were functionally distinct from T cells secreting the same cytokine in peripheral tissues. TFH cells with different cytokine profiles could be isolated as conjugates with B cells undergoing cytokine-specific immunoglobulin class-switching with evidence of somatic hypermutation. These findings subport a model wherein B cells compete for cytokines produced by TFH cells that shape the affinity and isotype of the antibody response.
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