A major deletion in the Vκ-Jκ intervening region results in hyperelevated transcription of proximal Vκ genes and a severely restricted repertoire

Our previous studies have shown that DNase I hypersensitive sites 1 and 2 (HS1-2) and HS3-6 within the mouse Vκ-Jκ intervening region are essential for controlling locus contraction and creating a diverse Ab repertoire. In this article, we demonstrate that a 6.3-κb deletion encompassing HS1-6 altogether not only leads to the predictable sums of these phenotypes, but also results in a novel hyperelevation of transcription of proximal Vk genes, in both pre-B and splenic B cells. These findings reveal previously unrecognized additional functions for cis-elements within the Vκ-Jκ intervening region, namely, prevention of the production of massive levels of noncoding RNA species by silencing transcription of germline proximal Vk genes in both developing and mature B cells.