Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

Nature | Dec 11, 2003

http://www.ncbi.nlm.nih.gov/pubmed/14668867

Regulated apoptosis is essential for both the development and the subsequent maintenance of the immune system. 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 identified. The antiapoptotic protein MCL-1 is an attractive candidate, as it is highly regulated, appears to enhance short-term survival and functions at an apical step in genotoxic deaths. However, Mcl-1 deficiency results in peri-implantation lethality. 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.

Pubmed ID: 14668867 RIS Download

Mesh terms: Alleles | Animals | Antigens, CD19 | Apoptosis | Attachment Sites, Microbiological | B-Lymphocytes | Cell Differentiation | Cell Lineage | Cell Survival | Cells, Cultured | Cytokines | Gene Deletion | Integrases | Mice | Myeloid Cell Leukemia Sequence 1 Protein | Neoplasm Proteins | Organ Specificity | Proto-Oncogene Proteins c-bcl-2 | RNA, Messenger | Spleen | Stem Cells | T-Lymphocytes | Thymus Gland | Viral Proteins

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

None

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.