B cells are programmed to activate kappa and lambda for rearrangement at consecutive developmental stages

kappa and lambda, the two types of immunoglobulin light (L) chains present in mammals, contribute differently to the L chain pool of each species. Her e we show that the extreme preponderance of kappa in the mouse results from programmed sequential activation of the kappa and lambda loci. Activation - a prerequisite of rearrangement - was monitored by analyzing transcriptio n of unrearranged J-C clusters. Upon in vitro differentiation of a rearrang ement-deficient pro/pre-B line, germ-line transcripts of the lambda J-C clu sters, that are newly described here, became detectable 2 days later than t heir counterparts of J-C kappa. Clear differences could also be observed in vivo: germ-line transcripts of kappa were already present in large B220(+) CD25(+) pre B-II cells whereas germ-line lambda transcripts first became d etectable at the consecutive developmental stage of small B220(+) CD25(+) p re-B-II cells. This activation pattern was found to be identical in mice wh ich can not rearrange kappa due to a targeted deletion or inactivation of k appa. This suggests that pre-B-II cells follow a hit-and-run mechanism of d evelopment which includes programmed transitions and differential activatio n of the L chain loci, ie. kappa first, then lambda. Thus, privileged activ ation of kappa might be the decisive factor in setting the 10:1 ratio of ka ppa to lambda present in the mouse.