| First Author | Broderick L | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 3644 |
| PubMed ID | 31409799 | Mgi Jnum | J:279373 |
| Mgi Id | MGI:6362312 | Doi | 10.1038/s41467-019-11570-6 |
| Citation | Broderick L, et al. (2019) Mutations in topoisomerase IIbeta result in a B cell immunodeficiency. Nat Commun 10(1):3644 |
| abstractText | 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. |
