Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells.
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Authors
Pae, JuheeErsching, Jonatan
Castro, Tiago B R
Schips, Marta
Mesin, Luka
Allon, Samuel J
Ordovas-Montanes, Jose
Mlynarczyk, Coraline
Melnick, Ari
Efeyan, Alejo
Shalek, Alex K
Meyer-Hermann, Michael

Victora, Gabriel D
Issue Date
2021-04-01
Metadata
Show full item recordAbstract
During affinity maturation, germinal center (GC) B cells alternate between proliferation and somatic hypermutation in the dark zone (DZ) and affinity-dependent selection in the light zone (LZ). This anatomical segregation imposes that the vigorous proliferation that allows clonal expansion of positively selected GC B cells takes place ostensibly in the absence of the signals that triggered selection in the LZ, as if by "inertia." We find that such inertial cycles specifically require the cell cycle regulator cyclin D3. Cyclin D3 dose-dependently controls the extent to which B cells proliferate in the DZ and is essential for effective clonal expansion of GC B cells in response to strong T follicular helper (Tfh) cell help. Introduction into the Ccnd3 gene of a Burkitt lymphoma-associated gain-of-function mutation (T283A) leads to larger GCs with increased DZ proliferation and, in older mice, clonal B cell lymphoproliferation, suggesting that the DZ inertial cell cycle program can be coopted by B cells undergoing malignant transformation.Citation
The Journal of Experimental Medicine. 2021 Apr;218(4). DOI: 10.1084/jem.20201699.Affiliation
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.Publisher
Rockefeller University PressPubMed ID
33332554Type
ArticleLanguage
enEISSN
1540-9538ae974a485f413a2113503eed53cd6c53
10.1084/jem.20201699
Scopus Count
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