The Mouse Immunoglobulin Kappa Light-Chain Genes Are Located in Early- and Late-Replicating Regions of Chromosome 6

Abstract

The murine immunoglobulin kappa (kappa) light-chain multigene family includes the constant region (C kappa), joining-region genes, and approximately 30 kappa-variable (V kappa) region families. The entire region occupies an estimated 1,000 to 3,000 kilobases, and some V kappa families have been linked by recombinant inbred mapping. The C kappa gene and 14 V kappa families replicated differently among cell lines of lymphoid and nonlymphoid origin. In nonlymphoid cells, the C kappa gene replicated earlier than the V kappa families. A transition from replication during the second third of S phase for the C kappa gene to later replication during S for V kappa families was observed. The V kappa family (V kappa 21) that maps closest to the C kappa gene, replicated during the first half of the S phase; most of the other V kappa families replicated during the second half of S, and some replicated during the last quarter of the S phase. In lymphoid cells, the kappa locus replicated earlier in the pre-B than in the B-cell lines. In one pre-B-cell line, 22D6, the kappa genes examined replicated at the beginning of the S phase. In the B-cell lines, the EcoRI segment containing the transcribed gene replicated near the beginning of the S phase. Other V kappa families replicated within the first two-thirds of S phase. Some linked V kappa families replicated at similar times. In the B-cell lines, a transition from replication at the beginning of S for the transcribed C kappa and V kappa genes and surrounding DNA sequences to later replication for the other V kappa families was observed. However, in contrast to the non-lymphoid cell lines, the replication of this locus occurred predominantly during the first half of S. The kappa locus contains both early- and late-replicating genes, and early replication is usually associated with transcriptional activity. The results are discussed with respect to the organization of transcriptionally active chromatin domains.