Centrioles are frequently amplified in early B cell development but dispensable for humoral immunity

Schapfl MA, LoMastro GM, Braun VZ, Hirai M, Levine MS, Kiermaier E, Labi V, Holland AJ, Villunger A (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 15

Article Number: 8890

Journal Issue: 1

DOI: 10.1038/s41467-024-53222-4

Abstract

Centrioles define centrosome structure and function. Deregulation of centriole numbers can cause developmental defects and cancer. The p53 tumor suppressor limits the growth of cells lacking or harboring additional centrosomes and can be engaged by the “mitotic surveillance” or the “PIDDosome pathway”, respectively. Here, we show that early B cell progenitors frequently present extra centrioles, ensuing their high proliferative activity and related DNA damage. Extra centrioles are efficiently cleared during B cell maturation. In contrast, centriole loss upon Polo-like kinase 4 (Plk4) deletion causes apoptosis and arrests B cell development. This defect can be rescued by co-deletion of Usp28, a critical component of the mitotic surveillance pathway, that restores cell survival and maturation. Centriole-deficient mature B cells are proliferation competent and mount a humoral immune response. Our findings imply that progenitor B cells are intolerant to centriole loss but permissive to centriole amplification, a feature potentially facilitating their malignant transformation.

Involved external institutions

Medizinische Universität Innsbruck AT Austria (AT) Johns Hopkins Hospital US United States (USA) (US) Kansai Medical University JP Japan (JP) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE)

How to cite

APA:

Schapfl, M.A., LoMastro, G.M., Braun, V.Z., Hirai, M., Levine, M.S., Kiermaier, E.,... Villunger, A. (2024). Centrioles are frequently amplified in early B cell development but dispensable for humoral immunity. Nature Communications, 15(1). https://doi.org/10.1038/s41467-024-53222-4

MLA:

Schapfl, Marina A., et al. "Centrioles are frequently amplified in early B cell development but dispensable for humoral immunity." Nature Communications 15.1 (2024).

BibTeX: Download