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Mutations in topoisomerase IIβ result in a B cell immunodeficiency

Lookup NU author(s): Dr Ian CowellORCiD, 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.

Publication metadata

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

Year: 2019

Volume: 10

Issue: 1

Online publication date: 13/08/2019

Acceptance date: 23/07/2019

Date deposited: 29/08/2019

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group


DOI: 10.1038/s41467-019-11570-6


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