Physical map of the human immunoglobulin K locus and its implications for the mechanisms of VK-JK rearrangement

Genomic regions containing numerous cloned VK genes (abbreviations in ref. 2) were investigated by pulsed-field gel electrophoresis. 31 and 32 genes were linked within 1.0 and 1.3 Mb NotI fragments, respectively; the latter fragment includes also the JKCK gene segment. A 0.25 Mb NotI fragment comprises further 10 VK genes. Since the transcriptional polarities of the VK genes within the genomic regions are known the linking of the regions allows us now to answer unequivocally some longstanding questions concerning the mechanism of VK-JK rearrangement. The VK genes of the 1.3 Mb NotI fragment except for the two JK proximal ones (accompanying paper) are arranged in the same transcriptional polarity as JKCK and therefore must rearrange by a deletion mechanism. The VK genes of the 1.0 Mb NotI fragment which has not yet been linked to VKJK have identical polarity within the fragment. They should be arranged in opposite polarity to JKCK since reciprocal recombination products derived from them are known to exist; such recombination products must have been formed by inversion of oppositely oriented gene segments.