Accessibility changes across the mouse Igh-V locus during B cell development

During their development, B and T lymphocytes are thought to undergo severa l cycles of chromatin remodeling at their antigen receptor loci that serve to regulate access of a common V(D)J recombinase to particular gene segment s. We used germ-line transcription and susceptibility to DNaseI as markers to examine tissue and stage-specific changes in chromatin structure surroun ding genes of the V(H)J558, V(H)10, and V(H)S107 families, whose members ar e located at discreet subregions of the locus. Germ-line VH transcripts fro m all three families were detectable at pro- and pre-B cell stages. Transcr ipts from the V(H)10 and V(H)S107 families, but not V(H)J558, remained dete ctable at the immature and mature B cell stages. Unexpectedly, none of the germ-line VH loci examined were markedly nuclease sensitive, regardless of cell type or transcriptional activity. A modest degree of nuclease sensitiv ity was noted at the V(H)J558 loci of pro-B and pre-B cells, however. Our d ata suggest that the entire Igh-V locus becomes accessible at early B cell stages, and returns thereafter to an inaccessible state. However, the timin g of these accessibility changes does not occur uniformly across the V-H ar ray. These results imply that multiple long-range elements are involved in targeting V-H genes for rearrangement.