Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells
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jem_20201699.pdf
Description
Published version
Size
7.95 MB
Format
Adobe PDF
Checksum (MD5)
029d0d237fc875460ac6d729f0529d9d
Author(s)
Pae, Juhee
Ersching, Jonatan
Castro, Tiago BR
Schips, Marta
Mesin, Luka
Allon, Samuel J
Ordovas-Montanes, Jose
Mlynarczyk, Coraline
Melnick, Ari
Efeyan, Alejo
Date Issued
2021
Journal
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Citation
Pae, Juhee, Ersching, Jonatan, Castro, Tiago BR, Schips, Marta, Mesin, Luka et al. 2021. "Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells." The Journal of Experimental Medicine, 218 (4).
Version
Final published version
Abstract
© 2020 Pae et al. 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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
Ragon Institute of MGH, MIT and Harvard
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1084/JEM.20201699
