Constitutive nuclear translocation of NF-kappa B in B cells in the absence of 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 constitutively active in these cells, in contrast with most other cell types. In the inactive form, NF-kappa B/Rel proteins are sequestered in the cytoplasm by members of the I kappa B family of NF-kappa B inhibitors. When activated, NF-kappa B is translocated to the nucleus, a process that involves the phosphorylation and proteasomal degradation of I kappa B proteins. Thus, NF-kappa B activation is accompanied by the rapid turnover of I kappa B proteins. 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 contain 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 10 times lower in IgG+ B cells than in IgM+ B cells, an additional indication 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 operates independently of I kappa B degradation. They further suggest that different isoforms of the B cell receptor may have distinct roles in regulating NF-kappa B activity.
Doerre
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Department of Microbiology, Boston University School of Medicine, MA 02118, USA. sdoerre@bu.edu
Corley
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D000818:Animals; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D020672:I-kappa B Proteins; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D016393:Lymphoma, B-Cell; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; C491366:Nfkbie protein, mouse; D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha; D051841:Transcription Factor RelB; D013755:Tetradecanoylphorbol Acetate