An unexpected immunoglobulin gene rearrangement, signal sequence replacement, was observed in which the recombinational signal sequences of a VH gene segment are fused intact to the 5′ end of a DJH element. Nudeotides are not lost from the signal sequences, but they may be lost from the DJH coding sequence. Signal sequence replacement may result from the alternative resolution of an intermediate in VH-to-DJH recombination. This type of rearrangement provides a means to alter the targeting of immunoglobulin gene segments and suggests a mechanism for the occurrence of VH-JH junctions in vivo. Signal sequence replacement may represent an additional pathway for the generation of antibody diversity.
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