A switch in distinct I kappa B alpha degradation mechanisms mediates constitutive NF-kappa B activation in mature B cells

Inducible activation of cytoplasmic NF-kappa B/Rel transcription factors oc curs via proteasome-dependent degradation of an associated inhibitor, terme d I kappa B alpha. Mature B lymphocytes constitutively express nuclear NF-k appa B, which is important for their long-term survival. The intrinsic mech anisms by which B cells constitutively activate NF-kappa B are unknown. In this paper we demonstrate that maintenance of NF-kappa B activity in primar y B cells is mediated by a novel calcium-dependent, but proteasome-independ ent, mechanism. Moreover, we show that differentiation of conditionally tra nsformed pre-B cells is accompanied by a switch from proteasome-dependent t o proteasome-independent degradation of I kappa B alpha. Our findings indic ate that I kappa B alpha degradation mechanisms are dynamic during B cell d evelopment, and ultimately establish constitutive NF-kappa B activity in ma ture B lymphocytes.