Constitutive Nuclear Translocation of NF-κB in B Cells in the Absence of IκB Degradation

Members of the NF-κB/Rel family of transcription factors are involved in many aspects of B lymphocyte development and function. NF-κB is constitutively active in these cells, in contrast with most other cell types. In the inactive form, NF-κB/Rel proteins are sequestered in the cytoplasm by members of the IκB family of NF-κB inhibitors. When activated, NF-κB is translocated to the nucleus, a process that involves the phosphorylation and proteasomal degradation of IκB proteins. Thus, NF-κB activation is accompanied by the rapid turnover of IκB proteins. We show that while this “classical” mode of NF-κB activation is a uniform feature of IgM+ B cell lines, all IgG+ B cells analyzed contain nuclear NF-κB yet have stable IκBα, IκBβ, and IκBε. Furthermore, Iκβε levels are at least 10 times lower in IgG+ B cells than in IgM+ B cells, an additional indication that the regulation of constitutive NF-κB activity in these two types of B cells is fundamentally different. These data imply the existence of a novel mechanism of NF-κB activation in IgG+ B cells that operates independently of IκB degradation. They further suggest that different isoforms of the B cell receptor may have distinct roles in regulating NF-κB activity.