Bcl11b is required for differentiation and survival of alphabeta T lymphocytes.
The gene Bcl11b, which encodes zinc finger proteins, and its paralog, Bcl11a, are associated with immune-system malignancies. We have generated Bcl11b-deficient mice that show a block at the CD4-CD8- double-negative stage of thymocyte development without any impairment in cells of B- or gammadelta T cell lineages. The Bcl11b-/- thymocytes showed unsuccessful recombination of V(beta) to D(beta) and lacked the pre-T cell receptor (TCR) complex on the cell surface, owing to the absence of Tcrb mRNA expression. In addition, we saw profound apoptosis in the thymus of neonatal Bcl11b-/- mice. These results suggest that Bcl11b is a key regulator of both differentiation and survival during thymocyte development.
Wakabayashi
Yuichi
Y
Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8122, Japan.
Watanabe
Hisami
H
Inoue
Jun
J
Takeda
Naoki
N
Sakata
Jun
J
Mishima
Yukio
Y
Hitomi
Jiro
J
Yamamoto
Takashi
T
Utsuyama
Masanori
M
Niwa
Ohtsura
O
Aizawa
Shinichi
S
Kominami
Ryo
R
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology; D020287:In Situ Nick-End Labeling; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D016335:Zinc Fingers / Q000235:genetics / Q000276:immunology; D018631:ras Proteins / Q000276:immunology*
D016692:Receptors, Antigen, T-Cell, gamma-delta; C472865:Rit1 protein, mouse; D018631:ras Proteins