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UBXN3B is crucial for B lymphopoiesisResearch in context

التفاصيل البيبلوغرافية
العنوان: UBXN3B is crucial for B lymphopoiesisResearch in context
المؤلفون: Tingting Geng, Duomeng Yang, Tao Lin, Andrew G. Harrison, Binsheng Wang, Ziming Cao, Blake Torrance, Zhichao Fan, Kepeng Wang, Yanlin Wang, Long Yang, Laura Haynes, Gong Cheng, Anthony T. Vella, Richard A. Flavell, Joao P. Pereira, Erol Fikrig, Penghua Wang
المصدر: EBioMedicine, Vol 106, Iss , Pp 105248- (2024)
بيانات النشر: Elsevier, 2024.
سنة النشر: 2024
المجموعة: LCC:Medicine
LCC:Medicine (General)
مصطلحات موضوعية: UBXN, Haematopoiesis, Lymphopoiesis, B cell, COVID-19, Medicine, Medicine (General), R5-920
الوصف: Summary: Background: The ubiquitin regulatory X (UBX) domain-containing proteins (UBXNs) are putative adaptors for ubiquitin ligases and valosin-containing protein; however, their in vivo physiological functions remain poorly characterised. We recently showed that UBXN3B is essential for activating innate immunity to DNA viruses and controlling DNA/RNA virus infection. Herein, we investigate its role in adaptive immunity. Methods: We evaluated the antibody responses to multiple viruses and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza in tamoxifen-inducible global and constitutive B cell-specific Ubxn3b knockout mice; quantified various immune populations, B lineage progenitors/precursors, B cell receptor (BCR) signalling and apoptosis by flow cytometry, immunoblotting and immunofluorescence microscopy. We also performed bone marrow transfer, single-cell and bulk RNA sequencing. Findings: Both global and B cell-specific Ubxn3b knockout mice present a marked reduction in small precursor B-II (>60%), immature (>70%) and mature B (>95%) cell numbers. Transfer of wildtype bone marrow to irradiated global Ubxn3b knockouts restores normal B lymphopoiesis, while reverse transplantation does not. The mature B population shrinks rapidly with apoptosis and higher pro and activated caspase-3 protein levels were observed following induction of Ubxn3b knockout. Mechanistically, Ubxn3b deficiency leads to impaired pre-BCR signalling and cell cycle arrest. Ubxn3b knockout mice are highly vulnerable to respiratory viruses, with increased viral loads and prolonged immunopathology in the lung, and reduced production of virus-specific IgM/IgG. Interpretation: UBXN3B is essential for B lymphopoiesis by maintaining constitutive pre-BCR signalling and cell survival in a cell-intrinsic manner. Funding: United States National Institutes of Health grants, R01AI132526 and R21AI155820.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2352-3964
Relation: http://www.sciencedirect.com/science/article/pii/S2352396424002846; https://doaj.org/toc/2352-3964
DOI: 10.1016/j.ebiom.2024.105248
URL الوصول: https://doaj.org/article/d87759c87aec46d69a881a5096e264fd
رقم الأكسشن: edsdoj.87759c87aec46d69a881a5096e264fd
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23523964
DOI:10.1016/j.ebiom.2024.105248