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dc.contributor.authorPae, Juhee
dc.contributor.authorErsching, Jonatan
dc.contributor.authorCastro, Tiago B R
dc.contributor.authorSchips, Marta
dc.contributor.authorMesin, Luka
dc.contributor.authorAllon, Samuel J
dc.contributor.authorOrdovas-Montanes, Jose
dc.contributor.authorMlynarczyk, Coraline
dc.contributor.authorMelnick, Ari
dc.contributor.authorEfeyan, Alejo
dc.contributor.authorShalek, Alex K
dc.contributor.authorMeyer-Hermann, Michael
dc.contributor.authorVictora, Gabriel D
dc.date.accessioned2021-01-07T11:00:27Z
dc.date.available2021-01-07T11:00:27Z
dc.date.issued2021-04-01
dc.identifier.citationThe Journal of Experimental Medicine. 2021 Apr;218(4). DOI: 10.1084/jem.20201699.en_US
dc.identifier.pmid33332554
dc.identifier.doi10.1084/jem.20201699
dc.identifier.urihttp://hdl.handle.net/10033/622666
dc.description.abstractDuring 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.en_US
dc.language.isoenen_US
dc.publisherRockefeller University Pressen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleCyclin D3 drives inertial cell cycling in dark zone germinal center B cells.en_US
dc.typeArticleen_US
dc.identifier.eissn1540-9538
dc.contributor.departmentBRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.en_US
dc.identifier.journalThe Journal of experimental medicineen_US
dc.rights.holder©2021 Pae et al. Originally published in he Journal of Experimental Medicine. https://doi.org/10.1084/jem.20201699
dc.source.volume218
dc.source.issue4
refterms.dateFOA2021-01-07T11:00:28Z
dc.source.journaltitleThe Journal of experimental medicine
dc.source.countryUnited States


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