Abstract
The effect of the B-cell chronic lymphocytic leukemia/lymphoma 11B gene (BCL11B) on human T-cell regulation remains unclear. To characterize the functions of BCL11B, recombinant BCL11B and BCL11B siRNA were transfected into human naive T cells to overexpress or knock down BCL11B expression, respectively. After BCL11B overexpression, the proliferation ability and the T-helper (Th) subset were increased, whereas no significant alteration in the expression pattern and clonality of the T-cell receptor Vβ subfamilies was observed. After BCL11B knockdown, a similar distribution of Vβ subfamilies was detected in the naive T cells; however, the proliferation capacity substantially decreased. Global gene expression profiling revealed that the dysregulated genes were mainly involved in T-cell activation and proliferation. BCL11B could selectively promote Th-cell differentiation because of increased CXCL10 and CXCL11 expression. BCL11B suppression may inhibit proliferation and induce apoptosis, which may relate to changes in the expression of CFLAR-CASP8-CASP10 in the mitochondrial pathways. In conclusion, BCL11B is required for T-cell survival; its overexpression could effectively increase the T-cell activation and proliferation abilities and Th-cell differentiation as well.
Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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CASP8 and FADD-Like Apoptosis Regulating Protein / genetics
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CASP8 and FADD-Like Apoptosis Regulating Protein / immunology
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Caspase 10 / genetics
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Caspase 10 / immunology
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Caspase 8 / genetics
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Caspase 8 / immunology
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Cell Proliferation
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Cell Survival
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Cells, Cultured
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Chemokine CXCL10 / genetics
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Chemokine CXCL10 / immunology
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Chemokine CXCL11 / genetics
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Chemokine CXCL11 / immunology
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Gene Expression / genetics
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Gene Expression / immunology*
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Gene Expression Profiling
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Gene Knockdown Techniques
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Humans
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Lymphocyte Activation
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Male
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Plasmids
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RNA, Small Interfering / genetics
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RNA, Small Interfering / immunology
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Repressor Proteins / genetics
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Repressor Proteins / immunology*
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Signal Transduction / genetics
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Signal Transduction / immunology*
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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Transfection
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / immunology*
Substances
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BCL11B protein, human
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CASP8 and FADD-Like Apoptosis Regulating Protein
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CFLAR protein, human
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CXCL10 protein, human
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Chemokine CXCL10
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Chemokine CXCL11
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RNA, Small Interfering
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Receptors, Antigen, T-Cell, alpha-beta
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Repressor Proteins
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Tumor Suppressor Proteins
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CASP8 protein, human
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Caspase 10
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Caspase 8
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CASP10 protein, human