期刊
SCIENCE
卷 349, 期 6248, 页码 643-646出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aac4919
关键词
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资金
- NIH Medical Scientist Training Program [T32GM07739]
- National Institute of Allergy and Infectious Diseases, NIH [1F30AI109903-01]
- NIH [AI037526-19, AI072529-06]
- NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [1UM1 AI100663-01]
- European Commission FP7 (Marie Curie Actions) [EMBOCOFUND2012, GA-2012-600394]
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.
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