MICE LACKING THE C-REL PROTOONCOGENE EXHIBIT DEFECTS IN LYMPHOCYTE-PROLIFERATION, HUMORAL IMMUNITY, AND INTERLEUKIN-2 EXPRESSION

The c-rel proto-oncogene, which is expressed predominantly in hemopoie tic cells encodes a subunit of the NF-kappa B-like family of transcrip tion factors. In mice with an inactivated c-rel gene, whereas developm ent of cells from all hemopoietic lineages appeared normal, humoral im munity was impaired and mature B and T cells were found to be unrespon sive to most mitogenic stimuli. Phorbol ester and calcium ionophore co stimulation, in contrast to certain membrane receptor-mediated signals , overcame the T cell-proliferative defect, demonstrating that T cell proliferation occurs by Rel-dependent and -independent mechanisms. The ability of exogenous interleukin-2 to restore T cell, but not B cell, proliferation indicates that Rel regulates the expression of differen t genes in B and T cells that are crucial for cell division and immune function.