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Lookup NU author(s): Dr Ian Cowell,
Professor Caroline AustinORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019, The Author(s).B cell development is a highly regulated process involving multiple differentiation steps, yet many details regarding this pathway remain unknown. Sequencing of patients with B cell-restricted immunodeficiency reveals autosomal dominant mutations in TOP2B. TOP2B encodes a type II topoisomerase, an essential gene required to alleviate topological stress during DNA replication and gene transcription, with no previously known role in B cell development. We use Saccharomyces cerevisiae, and knockin and knockout murine models, to demonstrate that patient mutations in TOP2B have a dominant negative effect on enzyme function, resulting in defective proliferation, survival of B-2 cells, causing a block in B cell development, and impair humoral function in response to immunization.
Author(s): Broderick L, Yost S, Li D, McGeough MD, Booshehri LM, Guaderrama M, Brydges SD, Kucharova K, Patel NC, Harr M, Hakonarson H, Zackai E, Cowell IG, Austin CA, Hugle B, Gebauer C, Zhang J, Xu X, Wang J, Croker BA, Frazer KA, Putnam CD, Hoffman HM
Publication type: Article
Publication status: Published
Journal: Nature Communications
Online publication date: 13/08/2019
Acceptance date: 23/07/2019
Date deposited: 29/08/2019
ISSN (electronic): 2041-1723
Publisher: Nature Publishing Group
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