2. Academic Validation
  3. Centrioles are frequently amplified in early B cell development but dispensable for humoral immunity

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

  • Nat Commun. 2024 Oct 15;15(1):8890. doi: 10.1038/s41467-024-53222-4.
Marina A Schapfl 1,  Gina M LoMastro 2,  Vincent Z Braun 1,  Maretoshi Hirai 3,  Michelle S Levine 2,  Eva Kiermaier 4,  Verena Labi 1,  Andrew J Holland 2,  Andreas Villunger 5 6
Affiliations

Affiliations

  • 1 Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
  • 2 Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • 3 Department of Pharmacology, Kansai Medical University, Hirakata, Osaka, Japan.
  • 4 Life and Medical Sciences Institute, Immune and Tumor Biology, University of Bonn, Bonn, Germany.
  • 5 Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria. andreas.villunger@i-med.ac.at.
  • 6 The Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria. andreas.villunger@i-med.ac.at.
PMID: 39406735 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.

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