TRANSIENT RESTORATION OF GENE REARRANGEMENT AT MULTIPLE T-CELL RECEPTOR LOCI IN GAMMA-IRRADIATED SCID MICE

The developmental arrest of thymocytes from scid mice, deficient in va riable, (diversity), and joining, or V(D)J recombination, can be overc ome by sublethal gamma-irradiation. Since previous studies focused on restoration of rearrangement of the T cell receptor (TCR) beta locus, productive rearrangement of which is selected for, we sought to examin e to what extent locus specificity and cellular selection contributed to the observed effects. We report here that irradiation of newborn sc id mice induces normal V-D-J rearrangements of the TCR delta locus, wh ich like TCR beta, is also actively rearranged in CD4(-)CD8(-) (double negative) thymocytes. In contrast, no complete V-J alpha rearrangemen ts were detected. Instead, we detected substantial levels of hairpin-t erminated coding ends at the 5' end of the J alpha locus, demonstratin g that TCR alpha rearrangements manifest the effects of the scid mutat ion. Irradiation, therefore, transiently compensates for the effects o f the scid mutation in a locus-nonspecific manner in thymocytes, resul ting in a burst of normal TCR beta and delta rearrangements. Irradiati on also allows the development of cells that can initiate but fail to complete V(D)J recombination events at the TCR alpha locus, which is n ormally inaccessible in scid thymocytes.