A HUMAN CATALYTIC ANTIBODY WITH THE LIGHT CHAIN RAISED BY SECONDARY VJ RECOMBINATION IN A HUMAN PLASMA CELL LINE

摘要

Immunoglobulin (Ig) gene rearrangements occur in a highly ordered fashion during B-cell development. Continuous rearrangement of the light chain genes has been reported in mature B cells in vivo, but not in Ig-secreting plasma cells. In our previous study, we have identified the antibody-secreting human plasma B-cell line HTD8, which actively replaces the production of the original lambda light chain with a new lambda chain at a high rate. In this study, we examined the peptidolytic activities of theantibodies produced by the plasma cell clones which have occurred secondary recombination to show a possible biological role of the newly-expressed antibodies. An antibody produced by one of the HTD8-derived cells had peptidolytic activities. As a result of sequence analysis, the variable region gene of the antibody light chain belonged to V_(lambda) 6 family. The other antibodies with the light chains belonging to V_(lambda) 6 family did not have such an activity. The difference among V_(lambda) 6-relating antibodies is a sequence diversification occurring in the combining site between variable and joint regions in the light chain. These results suggest that the peptidolytic activity of the antibody is gained by a sequence diversification occurring in the combining site between variable and joining regions in the light chain.