Antigen presentation by B cells enables epitope spreading across an MHC barrier.
Antigen presentation by B cells enables epitope spreading across an MHC barrier.
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DOI：
10.1038/s41467-023-42541-7
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发表时间：
2023-10-31
影响因子：
16.6
通讯作者：
Degn, Soren E.
中科院分区：
文献类型：
--
作者：
Fahlquist-Hagert, Cecilia;Wittenborn, Thomas R.;Terczynska-Dyla, Ewa;Kastberg, Kristian Savstrup;Yang, Emily;Rallistan, Alysa Nicole;Markett, Quinton Raymond;Winther, Gudrun;Fonager, Sofie;Voss, Lasse F.;Pedersen, Mathias K.;van Campen, Nina;Ferapontov, Alexey;Jensen, Lisbeth;Huang, Jinrong;Nieland, John D.;van der Poel, Cees E.;Palmfeldt, Johan;Carroll, Michael C.;Utz, Paul J.;Luo, Yonglun;Lin, Lin;Degn, Soren E.
间接证据表明，B细胞可能指示T细胞破坏耐受性。在这里，为了验证这一假设，我们使用了一个小鼠模型，其中一个单一的B细胞克隆沉淀类似系统性红斑狼疮（SLE）的自身反应性反应。起始克隆不需要进入生发中心来沉淀表位扩散。相反，它定位于滤泡外脾桥通道早期的反应。起始克隆产生的自身抗体不足以驱动自身反应性应答。随后的表位扩散依赖于抗原呈递，并由主要组织相容性复合体（MHC）进行区室化。携带两种MHC单倍型的B细胞可以在不共享MHC的B细胞之间桥接MHC屏障。因此，B细胞直接在MHC限制性T细胞的两个独立区室之间传递自身反应性，导致在生殖中心包含不同的B细胞群体。我们的研究结果表明，B细胞启动和传播的自身免疫反应。越来越多的证据表明B细胞的抗原呈递对于自身免疫的启动至关重要。在这里，作者证明了耐受性破坏是在生殖中心之外启动的，并且B细胞可以直接指导T细胞破坏耐受性并传播自身免疫反应。
Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. Here, to test this hypothesis, we used a murine model in which a single B cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating clone did not need to enter germinal centers to precipitate epitope spreading. Rather, it localized to extrafollicular splenic bridging channels early in the response. Autoantibody produced by the initiating clone was not sufficient to drive the autoreactive response. Subsequent epitope spreading depended on antigen presentation and was compartmentalized by major histocompatibility complex (MHC). B cells carrying two MHC haplotypes could bridge the MHC barrier between B cells that did not share MHC. Thus, B cells directly relay autoreactivity between two separate compartments of MHC-restricted T cells, leading to inclusion of distinct B cell populations in germinal centers. Our findings demonstrate that B cells initiate and propagate the autoimmune response. Increasing evidence suggests that antigen presentation by B cells is critical to the initiation of autoimmunity. Here, the authors demonstrate that tolerance breakdown is initiated outside of germinal centres and that B cells can directly instruct T cells to break tolerance and propagate autoimmune responses.
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DOI：
10.1126/science.aac4919
发表时间：
2015-08-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gitlin AD;Mayer CT;Oliveira TY;Shulman Z;Jones MJ;Koren A;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
56.9
作者：
Allen, Christopher D. C.;Okada, Takaharu;Cyster, Jason G.
通讯作者：
Cyster, Jason G.
捕获单小鼠生发中心之间克隆组成的变化。
影响因子：
7.7
作者：
Firl DJ;Degn SE;Padera T;Carroll MC
通讯作者：
Carroll MC
自动发芽中心的克隆进化。
影响因子：
64.5
作者：
Degn SE;van der Poel CE;Firl DJ;Ayoglu B;Al Qureshah FA;Bajic G;Mesin L;Reynaud CA;Weill JC;Utz PJ;Victora GD;Carroll MC
通讯作者：
Carroll MC
影响因子：
32.4
作者：
Berland, Robert;Fernandez, Luis;Imanishi-Kari, Thereza
通讯作者：
Imanishi-Kari, Thereza