MICE LACKING TDT - MATURE ANIMALS WITH AN IMMATURE LYMPHOCYTE REPERTOIRE

In adult animals, template-independent (or N) nucleotides are frequent ly added during the rearrangement of variable (V), diversity (D), and joining (J) segments of lymphocyte receptor genes, greatly enhancing j unctional diversity. Receptor genes from adult mice carrying a mutatio n in the terminal deoxynucleotidyl transferase (TdT) gene have few N n ucleotides, providing proof that this enzyme is essential for creating diversity. Unlike those from normal adults, receptor genes from adult mutant mice show extensive evidence of homology-directed recombinatio n, suggesting that TdT blocks this process. Thus, switch-on of the TdT gene during the first week after birth provokes an even greater expan sion of lymphocyte receptor diversity than had previously been thought .