A prematurely expressed Ig(kappa) transgene, but not V(kappa)J(kappa) gene segment targeted into the Ig(kappa) locus, can rescue B cell development in lambda5-deficient mice.

We generated surrogate light chain (SLC)-deficient mice carrying either a V(kappa)J(kappa)-C(kappa) transgene under the control of the kappa promoter and intron enhancer or a V(kappa)J(kappa) gene segment targeted into its physiological position. Efficient rescue of B cell development was seen in the former and partial rescue in the latter. This difference corresponded to a developmentally earlier onset of kappa chain expression from the conventional than from the targeted transgene. Thus, a kappa chain can substitute for SLC in development. However, mechanisms controlling gene expression in addition to gene rearrangements appear to restrict kappa chain expression largely to a cellular compartment into which mu chain-expressing B cell progenitors are selected with the help of the SLC.