@article{f1fe72948927478ca27debc914b42f9e,
title = "T cell help controls the speed of the cell cycle in germinal center B cells",
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.",
author = "Gitlin, \{Alexander D.\} and Mayer, \{Christian T.\} and Oliveira, \{Thiago Y.\} and Ziv Shulman and Jones, \{Mathew J. K.\} and Amnon Koren and Nussenzweig, \{Michel C.\}",
note = "We thank A. Miyawaki and T. Kurosaki for mice, T. Eisenreich for help with mouse colony management, K. Yao for technical help, J. Hurwitz and A. Farina for advice, B. Zhang and C. Zhao and the Rockefeller University Genomics Resource Center for assistance with high-throughput sequencing, K. Velinzon for assistance with cell sorting, and all members of the Nussenzweig laboratory for discussion. The data presented in this manuscript are tabulated in the main paper and in the supplementary materials. Supported by NIH Medical Scientist Training Program grant T32GM07739 and National Institute of Allergy and Infectious Diseases, NIH, grant 1F30AI109903-01 (A.D.G.); NIH grants AI037526-19 and AI072529-06 (M.C.N.); and the NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) 1UM1 AI100663-01 (M.C.N). Z.S. is a Human Frontiers of Science Program Fellow (reference LT000340/2011-L). C.T.M is an EMBO fellow (ALTF 456-2014) and is supported by the European Commission FP7 (Marie Curie Actions, EMBOCOFUND2012, GA-2012-600394). M.C.N. is an HHMI investigator. RNA sequencing data was deposited in the National Center for Biotechnology Information (NCBI), NIH, Gene Expression Omnibus (GEO) and is accessible through accession number GSE71295. Replication timing data was deposited in NCBI's Sequence Read Archive (SRA) and is accessible through accession number SRP061569.",
year = "2015",
month = aug,
day = "7",
doi = "10.1126/science.aac4919",
language = "الإنجليزيّة",
volume = "349",
pages = "643--646",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6248",
}