The E3 ubiquitin ligase Itch deficiency promotes antigen-driven B-cell responses in mice.,European Journal of Immunology

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The E3 ubiquitin ligase Itch deficiency promotes antigen-driven B-cell responses in mice.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-07-11 , DOI: 10.1002/eji.202048640
Ying Fang _{1,

2} , Youdi He _{1,

3} , Bing Zhai _{4,

5} , Chunmei Hou ₄ , Ruonan Xu ₁ , Chen Xing ₄ , Xiaoqian Wang ₆ , Ning Ma ₂ , Gencheng Han ₄ , Renxi Wang ₁

Affiliation

Deficiency of Itch, an E3 ubiquitin ligase, usually induced severe systemic and progressive autoimmune disease. The Itch function is well studied in T cells but not in B cells. We hypothesize that B‐cell‐specific Itch deficiency promoted antigen‐induced B‐cell activation and antibody‐expressing plasma cell (PC) production. We found that unlike Itch KO, Itch cKO (CD19^creItch^f/f) mice did not demonstrated a significant increase in the sizes of spleens and LNs, antibody level, and base mutation of antibody gene. However, in line with the fact that Itch expression decreased in GC B cells, PCs, and plasmablast (PB)‐like SP 2/0 cells, Itch deficiency promoted B‐cell activation and antibody production induced by antigens including lipopolysaccharide (LPS) and sheep red blood cells (SRBCs). Mechanistically, we found that Itch deficiency promotes antigen‐induced cytokine production because Itch controls the proteins (e.g., eIF3a, eIF3c, eIF3h) with translation initiation factor activity. Altogether, our data suggest that Itch deficiency promotes antigen‐driven B‐cell response. This may provide hints for Itch‐targeted treatment of patients with autoimmune disease.

中文翻译：

E3泛素连接酶瘙痒缺乏症会促进小鼠中抗原驱动的B细胞反应。

E3泛素连接酶Itch缺乏症通常诱发严重的全身性和进行性自身免疫性疾病。在T细胞中对Itch功能进行了很好的研究，而在B细胞中则没有。我们假设B细胞特异性瘙痒症促进了抗原诱导的B细胞活化和表达抗体的浆细胞（PC）的产生。我们发现与Itch KO不同，Itch cKO（CD19 ^cre Itch ^{f / f}）小鼠的脾脏和LN大小，抗体水平和抗体基因碱基突变均未显示出明显增加。但是，与Itch表达在GC B细胞，PC和成浆细胞（PB）样SP 2/0细胞中减少的事实相一致，Itch缺乏促进了B细胞的活化和由脂多糖（LPS）和绵羊红细胞（SRBC）。从机理上讲，我们发现Itch缺乏会促进抗原诱导的细胞因子的产生，因为Itch控制具有翻译起始因子活性的蛋白质（例如eIF3a，eIF3c，eIF3h）。总之，我们的数据表明，瘙痒缺乏症会促进抗原驱动的B细胞反应。这可能为以痒病为目标的自身免疫病患者治疗提供了提示。

更新日期：2020-07-11

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