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. Here 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 transcription of unrearranged J-C clusters. Upon in vitro differentiation of a rearrangement-deficient pro/pre-B line, germ-line transcripts of the lambda J-C clusters, that are newly described here, became detectable 2 days later than their 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 detectable at the consecutive developmental stage of small B220+ CD25+ pre-B-II cells. This activation pattern was found to be identical in mice which can not rearrange kappa due to a targeted deletion or inactivation of kappa. This suggests that pre-B-II cells follow a hit-and-run mechanism of development which includes programmed transitions and differential activation of the L chain loci, i.e. kappa first, then lambda. Thus, privileged activation of kappa might be the decisive factor in setting the 10:1 ratio of kappa to lambda present in the mouse.