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 variable, (diversity), and joining, or V(D)J recombination, can be overcome 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 examine to what extent locus specificity and cellular selection contributed to the observed effects. We report here that irradiation of newborn scid mice induces normal V-D-J rearrangements of the TCR delta locus, which like TCR beta, is also actively rearranged in CD(4-)CD(8-) (double negative) thymocytes. In contrast, no complete V-J alpha rearrangements were detected. Instead, we detected substantial levels of hairpin-terminated coding ends at the 5' end of the J alpha locus, demonstrating that TCR alpha rearrangements manifest the effects of the scid mutation. Irradiation, therefore, transiently compensates for the effects of the scid mutation in a locus-nonspecific manner in thymocytes, resulting in a burst of normal TCR beta and delta rearrangements. Irradiation 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 normally inaccessible in scid thymocytes.
Livák
F
F
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Welsh
S C
SC
Guidos
C J
CJ
Crispe
I N
IN
Danska
J S
JS
Schatz
D G
DG
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D005260:Female; D005720:Gamma Rays; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000528:radiation effects; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID / Q000276:immunology*; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011995:Recombination, Genetic; D015183:Restriction Mapping; D013950:Thymus Gland / Q000166:cytology
D011948:Receptors, Antigen, T-Cell