TARGETED DISRUPTION OF MU-CHAIN MEMBRANE EXON CAUSES LOSS OF HEAVY-CHAIN ALLELIC EXCLUSION

BURNET'S clonal selection theory 1 suggests that each B lymphocyte is committed to a single antibody specificity. This is achieved by a programme of somatic rearrangements of the gene segments encoding antibody variable (V) regions, in the course of B-cell development 2,3 . Evidence from immunoglobulin-transgenic mice and immunoglobulin-gene-transfected transformed pre-B cells suggests that the membrane form of the immunoglobulin heavy (H) chain of class-mu (mu-m), expressed from a rearranged H-chain (IgH) locus, may signal allelic exclusion of the homologous IgH locus in the cell 4-6 and initiation of light (L)-chain gene rearrangement in the Ig-kappa loci 6. We report here that targeted disruption of the membrane exon of the mu-chain indeed results in the loss of H-chain allelic exclusion. But, some kappa-chain gene rearrangement is still observed in the absence of mu-m expression.