T cell help controls the speed of the cell cycle in germinal center B cells.

TitleT cell help controls the speed of the cell cycle in germinal center B cells.
Publication TypeJournal Article
Year of Publication2015
AuthorsGitlin AD, Mayer CT, Oliveira TY, Shulman, iv Z, Jones MJK, Koren A, Nussenzweig MC
JournalScience
Date Published08/07/2015
ISSN1095-9203
Abstract

The germinal center (GC) is a microanatomical compartment wherein high-affinity antibody-producing B cells are selectively expanded. B cells proliferate and mutate their antibody genes in the dark zone (DZ) of the GC and are then selected by T cells in the light zone (LZ) on the basis of affinity. Here, we show that T cell help regulates the speed of cell cycle phase transitions and DNA replication of GC B cells. Genome sequencing and single-molecule analyses revealed that T cell help shortens S phase by regulating replication fork progression while preserving the relative order of replication origin activation. Thus, high-affinity GC B cells are selected by a mechanism that involves prolonged dwell time in the DZ where selected cells undergo accelerated cell cycles.

DOI10.1126/science.aac4919
Alternate JournalScience
PubMed ID26184917
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
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