Two new and unusual products of V(D)J recombination in lymphoid cells have been identified. Normal recombination joins the two signal sequences that identify the rearrangement site and, in the complementary reaction, joins the fragments of coding sequences that flank the signals. In extrachromosomal plasmid substrates, these products are found, but there is also a class of """"""""hybrid joints"""""""" that link one signal to the coding flank of its partner signal. A second class of """"""""open and shut"""""""" events rejoins each signal to its own flank, and is identifiable because of nucleotides lost and/or added at the joint. Both these products supply evidence that DNA strand alignment is not precisely specified in V(D)J recombination. A specific defect of V(D)J recombination has been identified in lymphoid cell lines derived from mice with the severe combined immune deficiency (scid) mutation. In extrachromosomal substrates, these cells make signal joints (though with greater imprecision than normal) but are unable to make coding joints. This failure appears sufficient to explain the absence of functional B and T cells in scid mice.
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