Abstract:
:T lymphocytes and B lymphocytes integrate activating signals to control the size of their proliferative response. Here we report that such control was achieved by timed changes in the production rate of cell-cycle-regulating proto-oncoprotein Myc, with division cessation occurring when Myc levels fell below a critical threshold. The changing pattern of the level of Myc was not affected by cell division, which identified the regulating mechanism as a cell-intrinsic, heritable temporal controller. Overexpression of Myc in stimulated T cells and B cells did not sustain cell proliferation indefinitely, as a separate 'time-to-die' mechanism, also heritable, was programmed after lymphocyte activation and led to eventual cell loss. Together the two competing cell-intrinsic timed fates created the canonical T cell and B cell immune-response pattern of rapid growth followed by loss of most cells. Furthermore, small changes in these timed processes by regulatory signals, or by oncogenic transformation, acted in synergy to greatly enhance cell numbers over time.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Heinzel S,Binh Giang T,Kan A,Marchingo JM,Lye BK,Corcoran LM,Hodgkin PDdoi
10.1038/ni.3598subject
Has Abstractpub_date
2017-01-01 00:00:00pages
96-103issue
1eissn
1529-2908issn
1529-2916pii
ni.3598journal_volume
18pub_type
杂志文章abstract::The ST2L receptor for interleukin 33 (IL-33) mediates pulmonary inflammation and immune system-related disorders, such as asthma and rheumatoid arthritis. At present, very little is known about the molecular regulation of ST2L expression. Here we found that FBXL19, an 'orphan' member of the Skp1-Cullin-F-box family of...
journal_title:Nature immunology
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journal_title:Nature immunology
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pub_type: 评论,新闻
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pub_type: 杂志文章
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更新日期:2008-08-01 00:00:00
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journal_title:Nature immunology
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2014-12-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2006-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/s41590-020-0641-5
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pub_type: 杂志文章,评审
doi:10.1038/ni.2018
更新日期:2011-06-01 00:00:00
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1123
更新日期:2004-11-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1038/ni.2284
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pub_type: 杂志文章
doi:10.1038/89800
更新日期:2001-07-01 00:00:00
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1563
更新日期:2008-03-01 00:00:00
abstract::We describe a protein with the hallmarks of a chemokine, designated CXCL16, that is made by dendritic cells (DCs) in lymphoid organ T cell zones and by cells in the splenic red pulp. CXCL16 contains a transmembrane domain and both membrane-bound and soluble forms are produced. Naïve CD8 T cells, natural killer T cells...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/79738
更新日期:2000-10-01 00:00:00
abstract::Caspases are important for apoptosis but are also involved in mammalian cell survival and cell division. Here we report that caspase-3 is a negative regulator of B cell cycling. Mice deficient in caspase-3 (Casp3-/- mice) have increased numbers of splenic B cells that show normal apoptosis but enhanced proliferation i...
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pub_type: 杂志文章
doi:10.1038/ni976
更新日期:2003-10-01 00:00:00
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journal_title:Nature immunology
pub_type: 杂志文章
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更新日期:2005-02-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1983
更新日期:2011-02-01 00:00:00
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3314
更新日期:2016-01-01 00:00:00
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pub_type: 杂志文章,已发布勘误
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更新日期:2018-08-01 00:00:00
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1502
更新日期:2007-09-01 00:00:00
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journal_title:Nature immunology
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2014-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2007-03-01 00:00:00