A Major Deletion in the V kappa-J kappa Intervening Region Results in Hyperelevated Transcription of Proximal V kappa Genes and a Severely Restricted Repertoire

作者：Xiang, Yougui; Park, Sung-Kyun; Garrard, William T.^*

来源：The Journal of Immunology, 2014, 193(7): 3746-3754.

DOI：10.4049/jimmunol.1401574

• B-CELL DEVELOPMENT
• LIGHT-CHAIN LOCUS
• V(D)J RECOMBINATION
• ANTIBODY REPERTOIRE
• SOMATIC HYPERMUTATION
• IMMUNOGLOBULIN GENES
• HYPERSENSITIVE SITES
• ALLELIC EXCLUSION
• SEQUENCE
• ENHANCER

Our previous studies have shown that DNase I hypersensitive sites 1 and 2 (HS1-2) and HS3-6 within the mouse V kappa-J kappa 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 V kappa genes, in both pre-B and splenic B cells. These findings reveal previously unrecognized additional functions for cis-elements within the V kappa-J kappa intervening region, namely, prevention of the production of massive levels of noncoding RNA species by silencing transcription of germline proximal V kappa genes in both developing and mature B cells.

• 出版日期2014-10-1
• 单位天津医科大学