Compromised counterselection by FAS creates an aggressive subtype of germinal center lymphoma.
Compromised counterselection by FAS creates an aggressive subtype of germinal center lymphoma.
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Fas的折衷反选择造成了一种侵袭性的生发中心淋巴瘤亚型。
DOI：
10.1084/jem.20201173
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发表时间：
2021-03-01
期刊：
影响因子：
--
通讯作者：
Muppidi JR
中科院分区：
文献类型：
--
作者：
Razzaghi R;Agarwal S;Kotlov N;Plotnikova O;Nomie K;Huang DW;Wright GW;Smith GA;Li M;Takata K;Yamadi M;Yao C;O'Shea JJ;Phelan JD;Pittaluga S;Scott DW;Muppidi JR
Fas在生发中心(GC)动态平衡中的作用存在争议。Razzaghi等人。表明Fas是GC的一种强大的细胞内在调节因子，它的缺失定义了GC来源的淋巴瘤的一种侵袭性亚型。Fas在生发中心(Gc)B细胞上高表达，在弥漫性大B细胞淋巴瘤(DLBCL)中有Fas突变的报道。虽然GC来源的DLBCL比其他类型的DLBCL有更好的总体预后，但一些病例是难治性的，其分子基础通常是未知的。我们表明，Fas是GC B细胞的一种强大的细胞内在调节因子，可能通过T滤泡辅助(TFH)细胞衍生的Fas配体促进光区细胞的死亡。在没有Fas的情况下，由于积聚了不能明显结合抗原的细胞，GC的克隆性更加多样化。Fas的改变最常见于GC来源的DLBCL，与不良的预后和TFH细胞的丰富有关，并与调节TFH-B细胞相互作用的hVEM和PD-L1缺乏共存。这项工作表明，Fas对于GC的动态平衡是至关重要的，并表明在GC中失去TFH介导的反选择是导致GC来源的淋巴瘤致死性的原因之一。
The role of Fas in germinal center (GC) homeostasis is controversial. Razzaghi et al. show that Fas is a strong cell-intrinsic regulator of the GC and that its loss defines an aggressive subtype of GC-derived lymphoma. Fas is highly expressed on germinal center (GC) B cells, and mutations of FAS have been reported in diffuse large B cell lymphoma (DLBCL). Although GC-derived DLBCL has better overall outcomes than other DLBCL types, some cases are refractory, and the molecular basis for this is often unknown. We show that Fas is a strong cell-intrinsic regulator of GC B cells that promotes cell death in the light zone, likely via T follicular helper (Tfh) cell–derived Fas ligand. In the absence of Fas, GCs were more clonally diverse due to an accumulation of cells that did not demonstrably bind antigen. FAS alterations occurred most commonly in GC-derived DLBCL, were associated with inferior outcomes and an enrichment of Tfh cells, and co-occurred with deficiency in HVEM and PD-L1 that regulate the Tfh–B cell interaction. This work shows that Fas is critically required for GC homeostasis and suggests that loss of Tfh-mediated counterselection in the GC contributes to lethality in GC-derived lymphoma.
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影响因子：
32.4
作者：
Mesin, Luka;Ersching, Jonatan;Victora, Gabriel D.
通讯作者：
Victora, Gabriel D.
影响因子：
82.9
作者：
Chapuy B;Stewart C;Dunford AJ;Kim J;Kamburov A;Redd RA;Lawrence MS;Roemer MGM;Li AJ;Ziepert M;Staiger AM;Wala JA;Ducar MD;Leshchiner I;Rheinbay E;Taylor-Weiner A;Coughlin CA;Hess JM;Pedamallu CS;Livitz D;Rosebrock D;Rosenberg M;Tracy AA;Horn H;van Hummelen P;Feldman AL;Link BK;Novak AJ;Cerhan JR;Habermann TM;Siebert R;Rosenwald A;Thorner AR;Meyerson ML;Golub TR;Beroukhim R;Wulf GG;Ott G;Rodig SJ;Monti S;Neuberg DS;Loeffler M;Pfreundschuh M;Trümper L;Getz G;Shipp MA
通讯作者：
Shipp MA
DOI：
10.4049/jimmunol.1700420
发表时间：
2018-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kotov DI;Kotov JA;Goldberg MF;Jenkins MK
通讯作者：
Jenkins MK
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1088/1742-5468/2008/10/p10008
发表时间：
2008-10-01
影响因子：
2.4
作者：
Blondel, Vincent D.;Guillaume, Jean-Loup;Lefebvre, Etienne
通讯作者：
Lefebvre, Etienne