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

Abstract

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 DNasel as markers to examine tissue and stage-specific changes in chromatin structure surrounding genes of the VHJ558, VH10, and VHS107 families, whose members 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 VHS107 families, but not VHJ558, 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 VHJ558 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.