Journal
SCIENCE
Volume 358, Issue 6360, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aao2602
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Funding
- Empire State Stem Cell Fund through New York State Department of Health (NYSDOH) [C023046]
- European Molecular Biology Organization (EMBO) long-term fellowship [ALTF 456-2014]
- European Commission Seventh Framework Programme (FP7) (Marie Curie Actions, EMBOCOFUND) [GA-2012-600394]
- NIH Medical Scientist Training Program [T32GM07739]
- National Institute of Allergy and Infectious Diseases (NAID) of the NIH [F30-AI109903-03]
- Aidsfonds Netherlands
- Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery [OPP1033115, OPP1124068]
- NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [1UM1 AI100663]
- NAID of the NIH [AI100148, AI037526]
- Robertson Foundation
- Rockefeller University
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B cells undergo rapid cell division and affinity maturation in anatomically distinct sites in lymphoid organs called germinal centers (GCs). Homeostasis is maintained in part by B cell apoptosis. However, the precise contribution of apoptosis to GC biology and selection is not well defined. We developed apoptosis-indicator mice and used them to visualize, purify, and characterize dying GC B cells. Apoptosis is prevalent in the GC, with up to half of all GC B cells dying every 6 hours. Moreover, programmed cell death is differentially regulated in the light zone and the dark zone: Light-zone B cells die by default if they are not positively selected, whereas dark-zone cells die when their antigen receptors are damaged by activation-induced cytidine deaminase.
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