A STAGE-SPECIFIC ENHANCER OF IMMUNOGLOBULIN J-CHAIN GENE IS INDUCED BY INTERLEUKIN-2 IN A PRESECRETOR B-CELL STAGE

Interleukin-2 (IL-2)-induced transcription of the J chain gene was use d as a model for analyzing cytokine regulation during B cell developme nt. To determine whether IL-2 signals are targeted to a J chain gene e nhancer as well as to its promoter, the sequences flanking the J chain gene were first examined for DNase I hypersensitivity. Of six sites i dentified, two strong ones, 7.5 kb upstream of the J chain gene, were found to be associated with an enhancer that is active only during the antigen-driven stages of B cell development. Further analyses of the enhancer in the IL-2-responsive presecretor BCL1 cells showed that the enhancer is activated at this stage by an IL-2 signal that functions by opening the enhancer chromatin and stimulating STATE to bind to a S TATE element critical for the enhancer induction. Moreover, after this early induction stage, the enhancer was shown to be constitutively op en and active in terminally differentiated plasma cells.