英国剑桥大学Natalie Burrows等研究人员发现,缺氧诱导因子1α活性的动态调节对于正常B细胞发育至关重要。 相关论文于2020年8月31日在线发表于《自然—免疫学》。
Title: Dynamic regulation of hypoxia-inducible factor-1α activity is essential for normal B cell development
Author: Natalie Burrows, Rachael J. M. Bashford-Rogers, Vijesh J. Bhute, Ana Pealver, John R. Ferdinand, Benjamin J. Stewart, Joscelin E. G. Smith, Mukta Deobagkar-Lele, Girolamo Giudice, Thomas M. Connor, Akimichi Inaba, Laura Bergamaschi, Sam Smith, Maxine G. B. Tran, Evangelia Petsalaki, Paul A. Lyons, Marion Espeli, Brian J. P. Huntly, Kenneth G. C. Smith, Richard J. Cornall, Menna R. Clatworthy, Patrick H. Maxwell
Issue&Volume: 2020-08-31
Abstract: B lymphocyte development and selection are central to adaptive immunity and self-tolerance. These processes require B cell receptor (BCR) signaling and occur in bone marrow, an environment with variable hypoxia, but whether hypoxia-inducible factor (HIF) is involved is unknown. We show that HIF activity is high in human and murine bone marrow pro-B and pre-B cells and decreases at the immature B cell stage. This stage-specific HIF suppression is required for normal B cell development because genetic activation of HIF-1α in murine B cells led to reduced repertoire diversity, decreased BCR editing and developmental arrest of immature B cells, resulting in reduced peripheral B cell numbers. HIF-1α activation lowered surface BCR, CD19 and B cell–activating factor receptor and increased expression of proapoptotic BIM. BIM deletion rescued the developmental block. Administration of a HIF activator in clinical use markedly reduced bone marrow and transitional B cells, which has therapeutic implications. Together, our work demonstrates that dynamic regulation of HIF-1α is essential for normal B cell development.
DOI: 10.1038/s41590-020-0772-8
Source: https://www.nature.com/articles/s41590-020-0772-8
Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex