RelB reduces thymocyte apoptosis and regulates terminal thymocyte maturation

Abstract

Thymocyte maturation is controlled by successive developmental checkpoints connected to the acquisition of a functional T cell receptor (TCR). During thymocyte selection, engagement of the TCR regulates the fine balance between death and survival signals. At the final stages of single-positive (SP) thymocyte maturation, the coupling of the TCR changes from death- to proliferation-inducing signals, a competence required for optimal effector functions in the periphery. We show here that in RelB mutant thymuses, thymocyte differentiation of CD24(-) SP cells is partially impaired. Competitive bone marrow reconstitution experiments show that this defect is constitutive to the lymphoid compartment. This is accompanied by an increased proportion of apoptotic thymocytes and a drastically reduced proliferation upon activation with anti-CD3 antibody/PMA stimulation. Thus, the RelB protein contributes to the quality of cell signaling in thymocytes by providing anti-apoptotic signals. These results suggest that in addition to its major role on the activation of antigen-presenting cell function, the RelB protein is intrinsically required for terminal thymocyte differentiation and activation.