Constitutive nuclear translocation of NF-kappa B in B cells in the absenceof I kappa B degradation

Members of the NF-kappa B/Rel family of transcription factors are involved in many aspects of B lymphocyte development and function. NF-kappa B is con stitutively active in these cells, in contrast with most other cell types. In the inactive form, NF-kappa B/Rel proteins are sequestered in the cytopl asm by members of the I kappa B family of NF-kappa B inhibitors, When activ ated, NF-kappa B is translocated to the nucleus, a process that involves th e phosphorylation and proteasomal degradation of I kappa B proteins. Thus, NF-kappa B activation is accompanied by the rapid turnover of I kappa B pro teins. We show that while this "classical" mode of NF-kappa B activation is a uniform feature of IgM(+) B cell lines, all IgG(+) B cells analyzed cont ain nuclear NF-kappa B yet have stable I kappa B alpha, I kappa B beta, and I kappa B epsilon. Furthermore, I kappa beta epsilon levels are at least 1 0 times lower in IgG(+) B cells than in IgM(+) B cells, an additional indic ation that the regulation of constitutive NF-kappa B activity in these two types of B cells is fundamentally different. These data imply the existence of a novel mechanism of NF-kappa B activation in IgG(+) B cells that opera tes independently of I kappa B degradation. They further suggest that diffe rent isoforms of the B cell receptor may have distinct roles in regulating NF-kappa B activity.