» Articles » PMID: 20595614

An Early T Cell Lineage Commitment Checkpoint Dependent on the Transcription Factor Bcl11b

Overview
Journal Science
Specialty Science
Date 2010 Jul 3
PMID 20595614
Citations 221
Authors
Affiliations
Soon will be listed here.
Abstract

The identities of the regulators that mediate commitment of hematopoietic precursors to the T lymphocyte lineage have been unknown. The last stage of T lineage commitment in vivo involves mechanisms to suppress natural killer cell potential, to suppress myeloid and dendritic cell potential, and to silence the stem cell or progenitor cell regulatory functions that initially provide T cell receptor-independent self-renewal capability. The zinc finger transcription factor Bcl11b is T cell-specific in expression among hematopoietic cell types and is first expressed in precursors immediately before T lineage commitment. We found that Bcl11b is necessary for T lineage commitment in mice and is specifically required both to repress natural killer cell-associated genes and to down-regulate a battery of stem cell or progenitor cell genes at the pivotal stage of commitment.

Citing Articles

T Cell Development: From T-Lineage Specification to Intrathymic Maturation.

Golzari-Sorkheh M, Yoganathan K, Chen E, Singh J, Zuniga-Pflucker J Adv Exp Med Biol. 2025; 1471:81-137.

PMID: 40067585 DOI: 10.1007/978-3-031-77921-3_4.


DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

Lessel I, Baresic A, Chinn I, May J, Goenka A, Chandler K Am J Hum Genet. 2025; 112(2):394-413.

PMID: 39798569 PMC: 11866971. DOI: 10.1016/j.ajhg.2024.12.012.


A timed epigenetic switch balances T and ILC lineage proportions in the thymus.

Pease N, Denecke K, Chen L, Gerges P, Kueh H Development. 2024; 151(23.

PMID: 39655434 PMC: 11664168. DOI: 10.1242/dev.203016.


A mutant BCL11B-N440K protein interferes with BCL11A function during T lymphocyte and neuronal development.

Okuyama K, Yamashita M, Koumoundourou A, Wiegreffe C, Ohno-Oishi M, Murphy S Nat Immunol. 2024; 25(12):2284-2296.

PMID: 39487351 DOI: 10.1038/s41590-024-01997-5.


BMP suppresses Wnt signaling via the Bcl11b-regulated NuRD complex to maintain intestinal stem cells.

Li Y, Wang X, Huang M, Wang X, Li C, Li S EMBO J. 2024; 43(23):6032-6051.

PMID: 39433900 PMC: 11612440. DOI: 10.1038/s44318-024-00276-1.


References
1.
Wakabayashi Y, Watanabe H, Inoue J, Takeda N, Sakata J, Mishima Y . Bcl11b is required for differentiation and survival of alphabeta T lymphocytes. Nat Immunol. 2003; 4(6):533-9. DOI: 10.1038/ni927. View

2.
Inoue J, Kanefuji T, Okazuka K, Watanabe H, Mishima Y, Kominami R . Expression of TCR alpha beta partly rescues developmental arrest and apoptosis of alpha beta T cells in Bcl11b-/- mice. J Immunol. 2006; 176(10):5871-9. DOI: 10.4049/jimmunol.176.10.5871. View

3.
Vosshenrich C, Garcia-Ojeda M, Samson-Villeger S, Pasqualetto V, Enault L, Goff O . A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127. Nat Immunol. 2006; 7(11):1217-24. DOI: 10.1038/ni1395. View

4.
Golonzhka O, Liang X, Messaddeq N, Bornert J, Campbell A, Metzger D . Dual role of COUP-TF-interacting protein 2 in epidermal homeostasis and permeability barrier formation. J Invest Dermatol. 2008; 129(6):1459-70. PMC: 2754722. DOI: 10.1038/jid.2008.392. View

5.
Kamimura K, Ohi H, Kubota T, Okazuka K, Yoshikai Y, Wakabayashi Y . Haploinsufficiency of Bcl11b for suppression of lymphomagenesis and thymocyte development. Biochem Biophys Res Commun. 2007; 355(2):538-42. DOI: 10.1016/j.bbrc.2007.02.003. View