Survival-independent function of NF-κ-B/Rel during late stages of thymocyte differentiation

Transcription factors of the NF-kappa B/Rel family are important mediators of extracellular signals. Their implication in positive selection of thymocytes is suggested by a defective thymic development in transgenic mice that over-express I kappa B in thymocytes. These mice exhibit an accumulation of an unusually prominent population of TCRhigh/CD4/CD8 double positive cells in the thymus and a dramatic reduction of CD4(+) and CD8(+) cells in the periphery. The present study addresses the role of NF-kappa B in survival and differentiation processes of maturing thymocytes using I kappa B/bcl-2 and I kappa B/HY double-transgenic mice. Neither the introduction of the anti-apoptosis gene bcl-2 nor the positively selecting background in female HY transgenic mice resulted in a rescue of the maturational defects observed in the thymus of I kappa B transgenic mice. Thus, rather than promoting survival the main role of NF-kappa B/Rel proteins during positive selection of thymocytes appears to be the mediation of differentiation signals. (C) 1998 Elsevier Science Ltd. All rights reserved.