IFN-GAMMA INDUCES THE KAPPA-INTRON ENHANCER VIA AN IFN-STIMULATED RESPONSE ELEMENT

IFN-gamma is a potent inducer of Ig kappa light chain gene transcripti on in 70Z/3 pre-B cells, but the mechanism of this induction has not b een elucidated. The kappa intron enhancer contains a sequence closely resembling the IFN-stimulated response element (ISRE), We have determi ned that the kappa intron enhancer is IFN-gamma inducible in 70Z/3 cel ls and that the ISRE is required for this induction, The kappa intron ISRE specifically bound IFN response factor-1 (IRF-1) and the constitu tively expressed IRF-2. This ISRE is a multifunctional motif that also binds the LPS-inducible factor kappa BF-A and is located within the k appa BS region, which confers B cell specific activity to this enhance r, However, since the expression of IRF-1 is not restricted to B cells , it must not be sufficient for the induction of kappa transcription, Furthermore, in the pre-B cell line 38B9, which is representative of a n earlier stage in pre-B cell development than the 70Z/3 cell line, th e kappa intron enhancer was not induced by IFN-gamma despite the activ ation of IRF-1, These findings suggest that IFN-gamma activation of ka ppa gene transcription during B cell maturation may be developmentally controlled by elements that restrict the activity of the ISRE within the context of the intron enhancer.