INDUCTION OF NUCLEAR FACTOR-KAPPA-B DURING PRIMARY B-CELL DIFFERENTIATION

We have investigated activation of nuclear factor-kappa B (NF-kappa B) in the process of primary B cell differentiation in vitro, In this sy stem, NF-kappa B is strongly induced when B cells develop from the pre -B cell to the immature B cell stage, Unlike the typical NF-kappa B ac tivation in response to exogenous stimuli, induction proceeds with a s low time course, NF-kappa B induction is only observed in B cells that undergo differentiation, not in Rag2-deficient cells, Nuclear DNA bin ding complexes predominantly comprise p50/RelA heterodimers and, to a lesser extent, c-Rel-containing dimers, The increase in NF-kappa B bin ding activity is accompanied by a slow and steady decrease in I kappa B beta protein levels, Interestingly, absolute RelA protein levels rem ain unaffected, whereas RelB and c-Rel synthesis is induced. The reaso n for preferential nuclear translocation of RelA complexes appears to be selective inhibition by the I kappa B beta protein, I kappa B beta can efficiently inhibit p50/RelA complexes, but has a much reduced abi lity to interfere with p50/c-Rel DNA binding both in vitro and in vivo , Interestingly, p50/RelB complexes are not at all targeted by I kappa B beta, and coimmunoprecipitation experiments show no evidence for an association of I kappa B beta and RelB in vivo. Consistent with these observations, I kappa B beta cotransfection can inhibit p50/RelA-medi ated trans-activation, but barely affects p50/RelB mediated trans-acti vation.