Uncovering the V(D)J recombinase

As any good high school student can tell you, normal developmental processes give rise to individuals in which each cell contains an identical copy of the genome present in the original, fertilized egg. This comfortable image of a static and inviolate genetic blueprint was shattered in the late 1970s, however, when Susumu Tonegawa and colleagues showed that the genes that encode immunoglobulin heavy and light chains have a different structure in embryonic cells from that found in tumors derived from B cells (see accompanying Commentary by Tonegawa, 2004). Over the next decade, it would emerge that developing B lymphocytes assemble immunoglobulin genes from widely scattered gene segments, using a somatic DNA rearrangement process known as V(D)J recombination (Figure 1), and that developing T cells play the same trick to assemble functional T cell receptor genes.