NORMAL JUNCTIONAL DIVERSIFICATION OF IMMUNE RECEPTORS IN P53-DEFICIENT MICE

One of the strategies that the immune system utilizes to generate Ab a nd TCR diversity is programmed imprecision of coding joint formation. This is accomplished by both nucleotide loss and random nucleotide add ition (N segments) to the termini of immune receptor coding segments b efore resolution, Although it has been known for more than a decade th at terminal deoxynucleotidyl transferase is the enzyme responsible for N segment addition, the enzymes responsible for nucleotide loss have not been identified. Recently, the p53 tumor suppressor protein was sh own to have an intrinsic exonuclease activity; we reasoned that p53 as an exonuclease might be responsible for coding end processing during V(D)J recombination. Thus, we examined nucleotide loss from Ig and TCR -beta coding joints in mice lacking p53. We find no significant differ ence in the degree of nucleotide loss in coding joints isolated from t hese animals as compared with littermate controls. Thus, we conclude t hat p53 does not play a role in removal of nucleotides from coding ter mini during V(D)J recombination. Additionally, recent evidence has sur faced suggesting that p53 may play an important checkpoint role in ear ly thymocyte differentiation, More specifically, it has been suggested that p53 is required to prevent thymocytes from maturing to the doubl e-positive stage in the absence of a functionally rearranged TCR-beta allele. Our data suggest that TCR-beta selection is not affected in p5 3-deficient, V(D)J rearrangement-proficient mice.