A Major Deletion in the Vκ–Jκ Intervening Region Results in Hyperelevated Transcription of Proximal Vκ Genes and a Severely Restricted Repertoire

Abstract

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-kb 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 Vκ 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 Vκ genes in both developing and mature B cells.