GENERATION OF NORMAL T-LYMPHOCYTES AND B-LYMPHOCYTES BY C-JUN DEFICIENT EMBRYONIC STEM-CELLS

To determine the potential roles of c-jun in lymphocyte development, we generated somatic chimeric mice by injecting homozygous c-jun mutant embryonic stem (ES) cells into blastocysts from recombination activating gene-2 (RAG-2)-deficient mice. Chimeric mice had poor restoration of thymocytes, but contained substantial numbers of mature T and a lymphocytes in the periphery. Stimulation of c-jun(-/-) 8 cells resulted in normal levels of proliferation and immunoglobulin secretion. Likewise, stimulation of c-jun(-/-) T cells resulted in essentially normal levels of IL-2R alpha expression, IL-2 secretion, and proliferation. We further showed that the relatively normal activation responses of the c-jun(-/-) T cells probably results from the fact that other members of the Jun family contribute to the bulk of the activator protein-1 (AP-1) complexes in normal T cells and, as a result, AP-1 complexes are found at relatively normal levels in c-jun(-/-) T cells.