Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response.
Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response.
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DOI：
10.1038/ncomms10281
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发表时间：
2016-01-05
影响因子：
16.6
通讯作者：
Kassiotis G
中科院分区：
文献类型：
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作者：
Merkenschlager J;Ploquin MJ;Eksmond U;Andargachew R;Thorborn G;Filby A;Pepper M;Evavold B;Kassiotis G
抗原受体多样性通过为具有适当抗原反应性的淋巴细胞的克隆选择提供基础来支持适应性免疫。目前的模型将免疫应答期间的T细胞克隆选择归因于T细胞受体（TCR）对外源肽或自身肽的亲和力。在这里，我们报告，克隆选择的CD 4 + T细胞也是由B细胞的外部调节。响应于病毒感染，根据与自身反应性相关的功能性亲合力，抗原特异性TCR库通过交错克隆型扩增而逐渐多样化。低亲合力T细胞克隆型的克隆扩增依赖于表达MHC II的B细胞的可用性，而B细胞的激活又会影响B细胞的扩增。B细胞克隆型多样化的CD4+ T细胞的反应，也接种疫苗或肿瘤的挑战，揭示了一个共同的效果。 在免疫应答期间，CD4+ T细胞库被认为以多样性为代价增加亲合力。在这里，作者表明，B细胞作为抗原呈递细胞促进低亲和力T细胞克隆的发展，在反应的后期使T细胞库多样化。
Antigen receptor diversity underpins adaptive immunity by providing the ground for clonal selection of lymphocytes with the appropriate antigen reactivity. Current models attribute T cell clonal selection during the immune response to T-cell receptor (TCR) affinity for either foreign or self peptides. Here, we report that clonal selection of CD4+ T cells is also extrinsically regulated by B cells. In response to viral infection, the antigen-specific TCR repertoire is progressively diversified by staggered clonotypic expansion, according to functional avidity, which correlates with self-reactivity. Clonal expansion of lower-avidity T-cell clonotypes depends on availability of MHC II-expressing B cells, in turn influenced by B-cell activation. B cells clonotypically diversify the CD4+ T-cell response also to vaccination or tumour challenge, revealing a common effect. During an immune response, CD4+ T cell repertoire is thought to increase in avidity at the expense of diversity. Here the authors show that B cells act as antigen-presenting cells to boost the development of low-avidity T cell clones, diversifying the T cell repertoire at late stages of the response.