Re-organization of the immunoglobulin kappa gene on both alleles is not an obligatory prerequisite for Ig lambda gene expression in human cells.

Re-arrangement and expression of the immunoglobulin (Ig) genes in B cells occurs under an ordered developmental control. The sequential model of Ig light chain exclusion predicts that only after non-productive re-organization or deletion of both Ig kappa alleles would re-arrangement of Ig lambda gene segments occur. To prove this model, we asked whether expression of Ig lambda light chains is always associated with rearrangement and/or deletion of both Ig kappa alleles in human cells. Therefore, we established human diploid B-cell clones in vitro that produce Ig lambda light chains. Southern blot analysis of the Ig kappa alleles revealed that three Ig lambda expressing cell lines (out of six Ig lambda+ cell lines tested) harbour one Ig kappa allele in germline configuration. Furthermore, a 1.5 kb RNA derived from the germline Ig kappa locus was detected by Northern blot hybridizations. The results implicate that the mechanism of Ig light chain exclusion is not precisely sequential and that it does not necessarily need re-arrangement or deletion of both Ig kappa alleles as a prerequisite for Ig lambda light chain expression in human cells.