Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1

Joseph T. Opferman, Anthony Letai, Caroline Beard, Mia D. Sorcinelli, Christy C. Ong and Stanley J. Korsmeyer ()
Additional contact information
Joseph T. Opferman: Harvard Medical School
Anthony Letai: Harvard Medical School
Caroline Beard: Harvard Medical School
Mia D. Sorcinelli: Harvard Medical School
Christy C. Ong: Harvard Medical School
Stanley J. Korsmeyer: Harvard Medical School

Nature, 2003, vol. 426, issue 6967, 671-676

Abstract: Abstract Regulated apoptosis is essential for both the development and the subsequent maintenance of the immune system1,2. Interleukins, including IL-2, IL-4, IL-7 and IL-15, heavily influence lymphocyte survival during the vulnerable stages of VDJ rearrangement and later in ensuring cellular homeostasis, but the genes specifically responsible for the development and maintenance of lymphocytes have not been identified3,4,5,6,7,8. The antiapoptotic protein MCL-1 is an attractive candidate, as it is highly regulated9, appears to enhance short-term survival10 and functions at an apical step in genotoxic deaths11. However, Mcl-1 deficiency results in peri-implantation lethality12. Here we show that mice conditional for Mcl-1 display a profound reduction in B and T lymphocytes when MCL-1 is removed. Deletion of Mcl-1 during early lymphocyte differentiation increased apoptosis and arrested the development at pro-B-cell and double-negative T-cell stages. Induced deletion of Mcl-1 in peripheral B- and T-cell populations resulted in their rapid loss. Moreover, IL-7 both induced and required MCL-1 to mediate lymphocyte survival. Thus, MCL-1, which selectively inhibits the proapoptotic protein BIM, is essential both early in lymphoid development and later on in the maintenance of mature lymphocytes.

Date: 2003
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature02067 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:426:y:2003:i:6967:d:10.1038_nature02067

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature02067

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().