biostudies-literature00440Ramezani-Rad PCancer Centers CouncilNIAID NIH HHSNCI NIH HHSNational Institutes of Health108403https://www.ebi.ac.uk/biostudies/studies/S-EPMC7714654biostudies-literatureUnknown33(7)Germinal center (GC) B cells surge in their proliferative capacity, which poses a direct risk for B cell malignancies. G1- to S-phase transition is dependent on the expression and stability of D-type cyclins. We show that cyclin D3 expression specifically regulates dark zone (DZ) GC B cell proliferation. B cell receptor (BCR) stimulation of GC B cells downregulates cyclin D3 but induces c-Myc, which subsequently requires cyclin D3 to exert GC expansion. Control of DZ proliferation requires degradation of cyclin D3, which is dependent on phosphorylation of residue Thr283 and can be bypassed by cyclin D3^T283A hyperstabilization as observed in B cell lymphoma. Thereby, selected GC B cells in the light zone potentially require disengagement from BCR signaling to accumulate cyclin D3 and undergo clonal expansion in the DZ.Cell reportsCyclin D3 Governs Clonal Expansion of Dark Zone Germinal Center B Cells.PMC7714654R01AI041649R01 AI041649R01 AI122344P30 CA030199Zhu ZRickert RCRamezani-Rad PChen C44falseCyclin D3 Governs Clonal Expansion of Dark Zone Germinal Center B Cells.Germinal center (GC) B cells surge in their proliferative capacity, which poses a direct risk for B cell malignancies. G1- to S-phase transition is dependent on the expression and stability of D-type cyclins. We show that cyclin D3 expression specifically regulates dark zone (DZ) GC B cell proliferation. B cell receptor (BCR) stimulation of GC B cells downregulates cyclin D3 but induces c-Myc, which subsequently requires cyclin D3 to exert GC expansion. Control of DZ proliferation requires degradation of cyclin D3, which is dependent on phosphorylation of residue Thr283 and can be bypassed by cyclin D3^T283A hyperstabilization as observed in B cell lymphoma. Thereby, selected GC B cells in the light zone potentially require disengagement from BCR signaling to accumulate cyclin D3 and undergo clonal expansion in the DZ.2020-01-01T00:00:00Z2020 Nov2024-10-15T23:17:13.647Z2021-02-20T03:03:49ZS-EPMC77146543320719410.1016/j.celrep.2020.108403