Sequential induction of NF-kappa B/Rel family proteins during B-cell terminal differentiation.
The NF-kappa B/Rel family of at least five transcription factor polypeptides is thought to function both as a developmental regulator in B cells and as a rapid response system in all cells. To examine this notion in more detail, we determined the protein contents of both the inducible and constitutive NF-kappa B/Rel activities in a pre-B-cell line, 70Z/3, and a mature B-cell line, WEHI 231. NF-kappa B p50/p65 is the major inducible nuclear complex after lipopolysaccharide or phorbol myristate acetate treatment of 70Z/3 cells. The constitutive and inducible complexes in WEHI 231 cells are mainly composed of p50 and Rel. The constitutive or induced activities are all sensitive to I kappa B-alpha, but this inhibitor is very short-lived in WEHI 231 cells, suggesting that the balance between synthesis and degradation of I kappa B-alpha determines whether a particular cell lineage has constitutive activity. A patterned expression of the NF-kappa B/Rel activator proteins emerges from an analysis of other B-lineage cell lines and splenic B cells: mainly p50 and p65 in pre-B (and non-B) cells, a predominance of Rel and p50 in mature B cells, and expression of p52 and RelB in plasmacytoma lines. This ordered pattern of regulators may reflect the requirement for expression of different genes during terminal B-cell differentiation because different combinations of NF-kappa B/Rel family members preferentially activate distinct kappa B sites in reporter constructs.
Liou
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HC
Rockfeller University, New York, New York 10021.
Sha
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WC
Scott
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ML
Baltimore
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D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D016899:Interferon-beta / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D014157:Transcription Factors
D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; C497594:Relb protein, mouse; D051996:Transcription Factor RelA; D014157:Transcription Factors; D051841:Transcription Factor RelB; D016899:Interferon-beta