Inducible transcription of the unrearranged κ constant region locus is a common feature of pre-B cells and does not require DNA or protein synthesis

Abstract

Transcription of unrearranged κ constant region (κ0) loci is dramatically induced in pre-B cells transformed by the Abelson murine leukemia virus when the cells are exposed to bacterial lipopolysaccharide (LPS). Transcriptional activity, detected both by accumulation of the 8-kilobase κ0 RNA product and by nuclear run-on measurements, is evident within a few hours after exposure to LPS and continues to increase over a 24-hr period. During this time, transcription of rearranged μ heavy-chain loci remains at the basal constitutive level. In accord with previous studies of the B-cell lymphoma 70Z/3, this transcriptional activation is accompanied by the appearance of a DNase I-hypersensitive site in the κ enhancer region but not by any detectable hypomethylation of the locus. Moreover, the present studies demonstrate that induction of κ transcription can occur in the absence of DNA or protein synthesis. These results have led us to propose a model in which an external signal such as LPS or a functionally equivalent lymphokine may initiate κ transcription in pre-B cells by modifying or overriding the activity of an enhancer-specific factor.