Inducing the loss of immunoglobulin λ light chain production and the rearrangement of a previously excluded allele in human plasma B cell lines with concanavalin A

Abstract

We investigated the expression of differential λ light chains in human B cell lines secreting immunoglobulin (Ig). When these cell lines were cultured with concanavalin A for a long period of time, a subpopulation of some but not all of these cell lines was induced to express new λ light chains replacing the original λ chain (light chain shifting). Production of the new λ chain, which replaces the original λ chain, results from a VJ rearrangement at a previously excluded allele and a dramatic reduction of the original λ chain transcript, although no difference was found in the level of heavy chain transcript. Recombination activating genes RAG-1 and RAG-2, which are normally expressed during specific early stages of lymphocyte development, were expressed in not only the light chain shifting-inducible lines but also in the non-inducible cells. Treatment of these Ig secreting cell lines with dibutyryl cAMP, which is known to enhance expression of the RAG genes, could not induce the creation of new λ light chain-producing cells from the inducible lines, suggesting that the expression of the two RAG genes is not sufficient for inducing new λ light chain production. Concanavalin A induced a gradual but significant production lost of the original λ chain in a subpopulation of the light chain shifting-inducible cells but not in the non-inducible cells. Association of new λ light chain production with loss of original λ chain raises the possibility that, when the RAG genes are expressed, concanavalin A may act on a novel intracellular mechanism controlling λ light chain allelic exclusion in these plasma cell lines.