Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells.
Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells.
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DOI：
10.7554/elife.83908
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发表时间：
2023-03-02
期刊：
影响因子：
7.7
通讯作者：
Grigorova IL
中科院分区：
文献类型：
--
作者：
Ke F;Benet ZL;Maz MP;Liu J;Dent AL;Kahlenberg JM;Grigorova IL
滤泡调节性T细胞(TFR)在支持高亲和力的外源抗原特异性体液反应的同时，限制自身抗体和自身免疫的发展。然而，TFR是否能直接抑制获得自身抗原的生发中心(GC)B细胞尚不清楚。此外，TFR对自身抗原的TCR特异性尚不清楚。我们的研究表明，核蛋白中含有转铁蛋白受体特异性抗原。将这些蛋白定位于小鼠中的抗原特异性B细胞，会触发具有免疫抑制特性的TFR的快速积累。然后，TFR对GC B细胞进行负性调节，主要是抑制获取核蛋白的GC B细胞，这表明TFR与GC B细胞的直接同源相互作用在控制效应性B细胞反应中发挥了重要作用。
Follicular regulatory T cells (Tfr) restrict development of autoantibodies and autoimmunity while supporting high-affinity foreign antigen-specific humoral response. However, whether Tfr can directly repress germinal center (GC) B cells that acquire autoantigens is unclear. Moreover, TCR specificity of Tfr to self-antigens is not known. Our study suggests that nuclear proteins contain antigens specific to Tfr. Targeting of these proteins to antigen-specific B cells in mice triggers rapid accumulation of Tfr with immunosuppressive characteristics. Tfr then exert negative regulation of GC B cells with predominant inhibition of the nuclear protein-acquiring GC B cells, suggesting an important role of direct cognate Tfr-GC B cells interactions for the control of effector B cell response.