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B in B Cells in the Absence of IB Degradation1
Department of Microbiology, Boston University School of Medicine, Boston, MA 02118
Members of the NF-
B/Rel family of transcription factors are
involved in many aspects of B lymphocyte development and function.
NF-B is constitutively active in these cells, in contrast with most
other cell types. In the inactive form, NF-B/Rel proteins are
sequestered in the cytoplasm by members of the IB family of NF-B
inhibitors. When activated, NF-B is translocated to the nucleus, a
process that involves the phosphorylation and proteasomal degradation
of IB proteins. Thus, NF-B activation is accompanied by the rapid
turnover of IB proteins. We show that while this "classical"
mode of NF-B activation is a uniform feature of IgM+ B
cell lines, all IgG+ B cells analyzed contain nuclear
NF-B yet have stable IB
, IBß, and IB
.
Furthermore, Iß 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-B
activity in these two types of B cells is fundamentally different.
These data imply the existence of a novel mechanism of NF-B
activation in IgG+ B cells that operates independently of
IB degradation. They further suggest that different isoforms of the
B cell receptor may have distinct roles in regulating NF-B
activity.
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