INDUCING THE LOSS OF IMMUNOGLOBULIN LAMBDA-LIGHT-CHAIN PRODUCTION ANDTHE REARRANGEMENT OF A PREVIOUSLY EXCLUDED ALLELE IN HUMAN PLASMA B-CELL LINES WITH CONCANAVALIN-A

We investigated the expression of differential lambda light chains in human B cell lines secreting immunoglobulin (Ig), When these cell line s mere cultured with concanavalin A for a long period of time, a subpo pulation of some but not all of these cell Lines was induced to expres s new lambda light chains replacing the original lambda chain (light c hain shifting), Production of the new lambda chain, which replaces the original lambda chain, results from a VJ rearrangement at a previousl y excluded allele and a dramatic reduction of the original lambda chai n transcript, although no difference was found in the level of heavy c hain transcript, Recombination activating genes RAG-1 and RAG-2, which are normally expressed during specific early stages of lymphocyte dev elopment, were expressed in not only the light chain shifting-inducibl e lines but also in the non-inducible cells, Treatment of these Ig sec reting cell lines with dibutyryl cAMP, which is known to enhance expre ssion of the RAG genes, could not induce the creation of new lambda Li ght chain-producing cells from the inducible lines, suggesting that th e expression of the two RAG genes is not sufficient for inducing new l ambda light chain production. Concanavalin A induced a gradual but sig nificant production lost of the original lambda chain in a subpopulati on of the light chain shifting-inducible cells but not in the non-indu cible cells, Association of new lambda light chain production with los s of original lambda chain raises the possibility that, when the RAG g enes are expressed, concanavalin A may act on a novel intracellular me chanism controlling lambda light chain allelic exclusion in these plas ma cell lines.