Induction of nuclear factor-kappa B during primary B cell differentiation.
We have investigated activation of nuclear factor-kappa B (NF-kappa B) in the process of primary B cell differentiation in vitro. In this system, NF-kappa B is strongly induced when B cells develop from the pre-B cell to the immature B cell stage. Unlike the typical NF-kappa B activation in response to exogenous stimuli, induction proceeds with a slow time course. NF-kappa B induction is only observed in B cells that undergo differentiation, not in Rag2-deficient cells. Nuclear DNA binding complexes predominantly comprise p50/RelA heterodimers and, to a lesser extent, c-Rel-containing dimers. The increase in NF-kappa B binding activity is accompanied by a slow and steady decrease in I kappa B beta protein levels. Interestingly, absolute RelA protein levels remain unaffected, whereas RelB and c-Rel synthesis is induced. The reason for preferential nuclear translocation of RelA complexes appears to be selective inhibition by the I kappa B beta protein. I kappa B beta can efficiently inhibit p50/RelA complexes, but has a much reduced ability to interfere with p50/c-Rel DNA binding both in vitro and in vivo. Interestingly, p50/RelB complexes are not at all targeted by I kappa B beta, and coimmunoprecipitation experiments show no evidence for an association of I kappa B beta and RelB in vivo. Consistent with these observations, I kappa B beta cotransfection can inhibit p50/RelA-mediated trans-activation, but barely affects p50/RelB mediated trans-activation.
Kistler
B
B
MSZ, Institut für Medizinische Strahlenkunde und Zellforschung, Universitat Würzburg, Germany.
Rolink
A
A
Marienfeld
R
R
Neumann
M
M
Wirth
T
T
D016475:3T3 Cells; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D001692:Biological Transport / Q000235:genetics; D019556:COS Cells; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000494:pharmacology; D013234:Stem Cells / Q000378:metabolism; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D014157:Transcription Factors
D046911:Macromolecular Substances; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D051996:Transcription Factor RelA; D014157:Transcription Factors; D051841:Transcription Factor RelB