Light chain shifting: identification of a human plasma cell line actively undergoing light chain replacement.

We identified an antibody-secreting human B-cell line (HTD8), which actively replaces the production of the original lambda light chain with a new lambda chain (light chain shifting) at a high rate. Loss of the original rearranged lambda light chain occurs by significantly reducing the amount of transcript expressed. Expression of the new lambda chain, which replaces the original lambda chain, occurs by rearranging new VJ segments on a previously excluded allele. V lambda gene usage of these new rearrangements are biased toward Vlambda4, Vlambda6, and Vlambda10 families, which are known to be the least frequently used. In striking contrast to the plasma cell phenotype, recombination activating genes, RAG-1 and RAG-2, were expressed in the HTD8 cells and were shown to be necessary, but insufficient for inducing expression of the new lambda chain. These results suggest that human plasma cells have the potential to actively undergo light chain replacement.