Cyclin D3 Governs Clonal Expansion of Dark Zone Germinal Center B Cells.

Cell Reports
Parham Ramezani-RadRobert C Rickert

Abstract

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 D3T283A 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.

Citations

Mar 16, 2021·STAR Protocols·Parham Ramezani-Rad, Robert C Rickert
Apr 20, 2021·Frontiers in Immunology·Rinako Nakagawa, Dinis Pedro Calado
Jul 27, 2021·Frontiers in Immunology·Theinmozhi ArulrajMichael Meyer-Hermann
Aug 3, 2021·Frontiers in Immunology·Noushin Mossadegh-KellerSandrine Roulland
Aug 12, 2021·Immunity·Clara Young, Robert Brink

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Methods Mentioned

BETA
PCR
flow cytometry

Software Mentioned

Graphpad
Gimp
GNU Image Manipulation
Prism

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