Bcl11b is required for differentiation and survival of αβ 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.