Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells

• DOI: 10.1084/jem.20201699
• Publication Date: 2020-12-18T21:51:55Z
• Authors: Juhee Pae; Jonatan Ersching; Tiago B.R. Castro; Marta Schips; Luka Mesin; Samuel J. Allon; Jose Ordovas-Mont...; Coraline Mlynarczyk; Ari Melnick; Alejo Efeyan; Alex K. Shalek; Michael Meyer-Her...; Gabriel D. Victora
• Keywords: Cyclin D3; Cyclin D2; Cyclin B; Cyclin D

During affinity maturation, germinal center (GC) B cells alternate between proliferation and somatic hypermutation in the dark zone (DZ) affinity-dependent selection light (LZ). This anatomical segregation imposes that vigorous allows clonal expansion of positively selected GC takes place ostensibly absence signals triggered LZ, as if by “inertia.” We find such inertial cycles specifically require cell cycle regulator cyclin D3. Cyclin D3 dose-dependently controls extent to which proliferate DZ is essential for effective response strong T follicular helper (Tfh) help. Introduction into Ccnd3 gene a Burkitt lymphoma–associated gain-of-function mutation (T283A) leads larger GCs with increased and, older mice, lymphoproliferation, suggesting program can be coopted undergoing malignant transformation.