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Jost, PJ; Weiss, S; Ferch, U; Gross, O; Mak, TW; Peschel, C; Ruland, J.
Bcl10/Malt1 signaling is essential for TCR-induced NF-kappaB activation in thymocytes but dispensable for positive or negative selection.
J Immunol. 2007; 178(2):953-960 Doi: 10.4049/jimmunol.178.2.953 [OPEN ACCESS]
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Jost Philipp

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During T cell development in the thymus, high-affinity/avidity TCR engagement induces negative selection by apoptosis, while lower affinity/avidity TCR interactions lead to positive selection and survival of thymocytes. Yet, the mechanisms that discriminate between positive and negative selection are not fully understood. One major regulator of survival and apoptosis in lymphoid cells is the transcription factor NF-kappaB. Several reports have indicated key roles for NF-kappaB in positive and negative selection. In peripheral T cells, TCR ligation activates NF-kappaB through a selective pathway that involves protein kinase Ctheta, Bcl10, and Malt1. While protein kinase Ctheta is dispensable for thymic TCR signaling, the molecular roles of Bcl10 and Malt1 in thymocytes have not been investigated. In the present study, we show that both Bcl10 and Malt1 are essential for TCR signaling in thymocytes as a genetic disruption of either molecule blocks TCR-induced NF-kappaB activation in these cells. To investigate the function of this pathway in thymic selection, we introduced the Bcl10 or Malt1 mutations into three well-established TCR transgenic mouse models. Surprisingly, using several in vivo or in vitro assays, we were unable to demonstrate a role for TCR-induced NF-kappaB activation in either positive or negative selection. Thus, while TCR signaling to NF-kappaB controls the activation of mature T cells, we suggest that this pathway is not involved in the positive or negative selection of thymocytes.
Find related publications in this database (using NLM MeSH Indexing)
Adaptor Proteins, Signal Transducing - deficiency
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Animals -
Apoptosis -
B-Cell CLL-Lymphoma 10 Protein -
Caspases - deficiency
Caspases - genetics
Caspases - metabolism
Cells, Cultured -
Mice -
Mice, Knockout -
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein -
NF-kappa B - metabolism
Neoplasm Proteins - deficiency
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Receptors, Antigen, T-Cell - immunology
Receptors, Antigen, T-Cell - metabolism
Signal Transduction -
T-Lymphocytes - cytology
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Thymus Gland - metabolism

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