Loss of runx1 function results in B cell immunodeficiency but not T cell in adult zebrafish.
Loss of runx1 function results in B cell immunodeficiency but not T cell in adult zebrafish.
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runx1 功能丧失会导致成年斑马鱼 B 细胞免疫缺陷，但不会导致 T 细胞免疫缺陷
DOI：
10.1098/rsob.180043
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发表时间：
2018-07
期刊：
影响因子：
5.8
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Chi Y;Huang Z;Chen Q;Xiong X;Chen K;Xu J;Zhang Y;Zhang W
转录因子RUNX 1在多系造血中起着不可或缺的作用，并在淋巴细胞发育过程中作为V（D）J重排的辅助因子。Runx 1缺陷导致小鼠淋巴细胞不成熟和减少。在本研究中，我们发现runx 1 W84 X/W84 X突变导致B细胞减少和无序，以及B细胞而不是T细胞中的V（D）J重排失败，导致成年斑马鱼抗体不足介导的免疫缺陷。相反，T细胞发育不受影响。B细胞数量减少主要是由于未成熟B细胞过度凋亡所致。B细胞发育中断导致runx 1 W 84 X/W 84 X突变体表现出与常见可变免疫缺陷相似的表型--常见可变免疫缺陷是一种原发性免疫缺陷疾病，其主要特征是对感染的频繁易感性和免疫反应缺陷，IgG、伊加和/或IgM抗体产生显着减少。我们的研究证实了runx 1在成年斑马鱼B细胞成熟和分化过程中的进化保守功能，这将为免疫缺陷病及其治疗的研究提供一个有价值的模型。
Transcription factor RUNX1 holds an integral role in multiple-lineage haematopoiesis and is implicated as a cofactor in V(D)J rearrangements during lymphocyte development. Runx1 deficiencies resulted in immaturity and reduction of lymphocytes in mice. In this study, we found that runx1W84X/W84X mutation led to the reduction and disordering of B cells, as well as the failure of V(D)J rearrangements in B cells but not T cells, resulting in antibody-inadequate-mediated immunodeficiency in adult zebrafish. By contrast, T cell development was not affected. The decreased number of B cells mainly results from excessive apoptosis in immature B cells. Disrupted B cell development results in runx1W84X/W84X mutants displaying a similar phenotype to common variable immunodeficiency—a primary immunodeficiency disease primarily characterized by frequent susceptibility to infection and deficient immune response, with marked reduction of antibody production of IgG, IgA and/or IgM. Our studies demonstrated an evolutionarily conserved function of runx1 in maturation and differentiation of B cells in adult zebrafish, which will serve as a valuable model for the study of immune deficiency diseases and their treatments.
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DOI：
10.1056/nejmoa1512234
发表时间：
2016-03-17
期刊：
The New England journal of medicine
影响因子：
--
作者：
Kuehn HS;Boisson B;Cunningham-Rundles C;Reichenbach J;Stray-Pedersen A;Gelfand EW;Maffucci P;Pierce KR;Abbott JK;Voelkerding KV;South ST;Augustine NH;Bush JS;Dolen WK;Wray BB;Itan Y;Cobat A;Sorte HS;Ganesan S;Prader S;Martins TB;Lawrence MG;Orange JS;Calvo KR;Niemela JE;Casanova JL;Fleisher TA;Hill HR;Kumánovics A;Conley ME;Rosenzweig SD
通讯作者：
Rosenzweig SD
影响因子：
5.6
作者：
Link, Kevin A.;Chou, Fu-Sheng;Mulloy, James C.
通讯作者：
Mulloy, James C.
影响因子：
20.3
作者：
Balla, Keir M.;Lugo-Villarino, Geanncarlo;Traver, David
通讯作者：
Traver, David
影响因子：
10.5
作者：
Gyoery, Ildiko;Boller, Soeren;Grosschedl, Rudolf
通讯作者：
Grosschedl, Rudolf
影响因子：
32.4
作者：
Kwon, Kyongrim;Hutter, Caroline;Busslinger, Meinrad
通讯作者：
Busslinger, Meinrad