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During B cell development, discrete domains within the Igh locus are activated independently for recombination. The D-distal V(H) genes are uniquely dependent on IL-7R signaling, which is thought to establish local chromatin accessibility through an unknown mechanism. To dissect this mechanism, we used a murine B cell line that responds to IL-7 by specifically inducing accessibility of a representative D-distal gene (A1) but not a D-proximal gene (V11). We demonstrate that IL-7-activated Stat5 is recruited rapidly to the A1 gene, with a concomitant increase in germline transcription and H4 acetylation. Furthermore, retroviral transduction of dominant negative or constitutively active Stat5 demonstrated that Stat5 activation is both necessary and sufficient for the IL-7-induced A1 germline transcription. Lastly, as with all known Stat5 target genes, A1 germline transcription requires a deacetylase activity. These results demonstrate that in response to IL-7 signaling, Stat5 is recruited to the D-distal A1 gene and induces accessibility.

Cutting Edge: Stat5 Mediates the IL-7-Induced Accessibility of a Representative D-Distal VH Gene