Follicular regulatory T cells produce neuritin to regulate B cells
Follicular regulatory T cells produce neuritin to regulate B cells
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DOI：
10.1016/j.cell.2021.02.027
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发表时间：
2021-04-01
期刊：
影响因子：
64.5
通讯作者：
Vinuesa, Carola G.
中科院分区：
文献类型：
--
作者：
Gonzalez-Figueroa, Paula;Roco, Jonathan A.;Vinuesa, Carola G.
调节性T细胞可以防止自身抗体和过量IgE的出现，但确切的机制尚不清楚。在这里，我们表明，BCL-6表达Tfr，称为滤泡调节性T（Tfr）细胞，产生丰富的神经肽蛋白的目标B细胞。在Foxp 3表达细胞中缺乏Tfr细胞或neuritin的小鼠在生殖中心（GC）积累早期浆细胞，并产生针对组蛋白和组织特异性自身抗原的自身抗体。在免疫后，这些小鼠也产生增加的血浆IgE和IgG 1。我们表明，neuritin是采取了B细胞，导致磷酸化的许多蛋白质，并抑制IgE类转换。Neuritin减少小鼠和人GC B细胞向浆细胞的分化，下调BLIMP-1，上调BCL 6。给转铁蛋白缺乏的小鼠施用神经肽可防止早期浆细胞在GC中的积累。由Tfr细胞产生神经突素作为抑制B细胞驱动的自身免疫和IgE介导的过敏的中心机制出现。
Regulatory T cells prevent the emergence of autoantibodies and excessive IgE, but the precise mechanisms are unclear. Here, we show that BCL6-expressing Tregs, known as follicular regulatory T (Tfr) cells, produce abundant neuritin protein that targets B cells. Mice lacking Tfr cells or neuritin in Foxp3-expressing cells accumulated early plasma cells in germinal centers (GCs) and developed autoantibodies against histones and tissue-specific self-antigens. Upon immunization, these mice also produced increased plasma IgE and IgG1. We show that neuritin is taken up by B cells, causes phosphorylation of numerous proteins, and dampens IgE class switching. Neuritin reduced differentiation of mouse and human GC B cells into plasma cells, downregulated BLIMP-1, and upregulated BCL6. Administration of neuritin to Tfr-deficient mice prevented the accumulation of early plasma cells in GCs. Production of neuritin by Tfr cells emerges as a central mechanism to suppress B cell-driven autoimmunity and IgE-mediated allergies.