Control of gene rearrangements in lymphocytes has been studied. We looked for the signal in the thymic microenvironment that induces rearrangement of the TCRbeta gene. We identified the sign as interleukin 7, which induced expression of the RAG genes, leading to rearrangement. We identified CD-16 as a surface receptor that turns off rearrangement and diverts pre-T cells into the NK lineage. To identify the proteins that cut and splice the TCRbeta gene during rearrangement, we analyzed nuclear extracts from pre-T cells. A protein was identified that binds to the TCRbeta gene in regions thought to be involved in rearrangement, and this protein may be the DNA-binding component of a recombinase compled. The physiological role of IL 1 is being studied by creating mice that lack IL 1 as a result of gene targeting. We have created chimeric mice that carry a targeted IL 1beta allele and are in the course of establishing this in the germ line. In addition to IL 1-deficient mice, transgenic mice are also being produced. Mice carrying a transgene expressing anti- sense IL 1 receptor in the thymus showed preliminary evidence of a block in T cell development, suggesting a requirement for IL 1 in thymopoiesis. Transgenes that overexpress IL 1beta were generally found to be lethal during embryogenesis. Expression of precursor IL 1beta was found to kill several cell lines. Mice hav been produced with a transgene designed to overexpress IL 1 receptor antagonist.
