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An Essential Role of UBXN3B in B Lymphopoiesis
bioRxiv - Immunology Pub Date : 2021-08-24 , DOI: 10.1101/2021.03.04.433919
Tingting Geng , Duomeng Yang , Tao Lin , Andrew G Harrison , Binsheng Wang , Blake Torrance , Kepeng Wang , Yanlin Wang , Long Yang , Laura Haynes , Gong Cheng , Anthony T. Vella , Erol Fikrig , PENGHUA WANG

Hematopoiesis is finely regulated to enable timely production of the right numbers and types of mature immune cells to maintain tissue homeostasis. Dysregulated hematopoiesis may compromise antiviral immunity and/or exacerbate immunopathogenesis. Herein, we report an essential role of UBXN3B in maintenance of hematopoietic homeostasis and restriction of immunopathogenesis during respiratory viral infection. Ubxn3b deficient (Ubxn3b−/−) mice are highly vulnerable to SARS-CoV-2 and influenza A infection, characterized by more severe lung immunopathology, lower virus-specific IgG, significantly fewer B cells, but more myeloid cells than Ubxn3b+/+ littermates. This aberrant immune compartmentalization is recapitulated in uninfected Ubxn3b−/− mice. Mechanistically, UBXN3B controls precursor B-I (pre-BI) transition to pre-BII and subsequent proliferation in a cell-intrinsic manner, by maintaining BLNK protein stability and pre-BCR signaling. These results reveal an essential role of UBXN3B for the early stage of B cell development.

中文翻译:

UBXN3B 在 B 淋巴细胞生成中的重要作用

对造血功能进行精细调节,以便及时产生正确数量和类型的成熟免疫细胞,以维持组织稳态。造血功能失调可能会损害抗病毒免疫和/或加剧免疫发病机制。在此,我们报告了 UBXN3B 在呼吸道病毒感染期间维持造血稳态和限制免疫发病机制中的重要作用。Ubxn3b缺陷型 ( Ubxn3b -/- ) 小鼠极易受到 SARS-CoV-2 和甲型流感的感染,其特点是肺免疫病理学更严重,病毒特异性 IgG 较低,B 细胞明显减少,但骨髓细胞比Ubxn3b +/+ 多同窝仔。这种异常的免疫区室化在未感染的Ubxn3b -/-小鼠。从机制上讲,UBXN3B 通过维持 BLNK 蛋白稳定性和 pre-BCR 信号传导,以细胞内在方式控制前体 BI(pre-BI)向 pre-BII 的转变和随后的增殖。这些结果揭示了 UBXN3B 在 B 细胞发育的早期阶段的重要作用。
更新日期:2021-08-26
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