A human immunoglobulin lambda locus is similarly well expressed in mice and humans

Transgenic mice carrying a 380-kb region of the human immunoglobulin (Ig) l ambda light (L) chain locus in germline configuration were created. The int roduced translocus on a yeast artificial chromosome (YAC) accommodates the most proximal Ig lambda variable region (V) gene cluster, including 15 V la mbda genes that contribute to >60% of lambda L chains in humans, all J lamb da-C lambda segments, and the 3' enhancer. HuIg lambda YAC mice were bred w ith animals in which mouse Ig kappa production was silenced by gene targeti ng. In the K-/- background, human Ig lambda was ex-pressed by similar to 84 % of splenic B cells. A striking result was that human Ig lambda was also p roduced at high levels in mice with normal kappa locus. Analysis of bone ma t-row cells showed that human Ig lambda and mouse Ig kappa were expressed a t similar levels throughout B cell development, suggesting that the Ig lamb da translocus and the endogenous kappa locus rearrange independently and wi th equal efficiency at the same developmental stage. This is further suppor ted by the finding that in hybridomas expressing human Ig lambda the endoge nous L chain loci were in germline configuration. The presence of somatic h ypermutation in the human V lambda genes indicated that the Ig lambda-expre ssing cells function normally. The finding that human lambda genes can be u tilized with similar efficiency in mice and humans implies that L chain exp ression is critically dependent on the configuration of the locus.