STUDIES OF IMMUNOGLOBULIN GENE REARRANGEMENT

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Our earlier work on antigen receptor gene rearrangement (V(D)J recombination) described one type of broken DNA molecules that were plausible intermediates in this process. These molecules, seen at the T cell receptor delta locus (TCR), had only the free end containing the recombination signal sequence. We have now also been able to find broken molecules with the end of the coding sequence, but only in DNA from mice with the scid mutation, which interferes with the joining of these ends. The coding ends are found to have an abnormal structure: the two DNA strands are linked to each other in a hairpin configuration.The presence of hairpins offers a good explanation for the observation, in immunoglobulin and T cell receptor coding junctions, of self- complementary sequences formed during recombination. If a hairpin structure is nicked off-center, a self- complementary insertion will naturally result. These results strengthen the evidence for a breakage-reunion model of V(D)J recombination, but also indicate that the process must be different from earlier examples of this type.