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

During their development, B and T lymphocytes are thought to undergo several cycles of chromatin remodeling at their antigen receptor loci that serve to regulate access of a common V(D)J recombinase to particular gene segments. We used germ‐line transcription and susceptibility to DNaseI as markers to examine tissue and stage‐specific changes in chromatin structure surrounding genes of the VH J558, VH10, and VH S107 families, whose mem bers are located at discreet subregions of the locus. Germ‐line VH transcripts from all three families were detectable at pro‐ and pre‐B cell stages. Transcripts from the VH10 and VH S107 families, but not VH J558, remained detectable 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 sensitivity was noted at the VH J558 loci of pro‐B and pre‐B cells, however. Our data suggest that the entire Igh‐V locus becomes accessible at early B cell stages, and returns thereafter to an inaccessible state. However, the timing of these accessibility changes does not occur uniformly across the VH array. These results imply that multiple long‐range elements are involved in targeting VH genes for rearrangement.