The subunit composition of NF-kappa B complexes changes during B-cell development.
The transcription factor NF-kappa B, shown to be essential for expression of the immunoglobulin C kappa gene, is a key regulatory component in pre-B to B-cell differentiation. While previous studies have used lymphoid cell line models, here we examine the expression and subunit composition of rel/NF-kappa B complexes in normal murine pre-B and B lymphocytes. Two major NF-kappa B complexes are detected in pre-B and B cells. A high mobility complex, found in pre-B (Cb) and B cells (C beta) is a homodimer of the NF-kappa B subunit p50. In pre-B cells, the slower migrating complex (Ca), which is predominantly cytoplasmic, is largely comprised of p50 and p65, whereas in B cells, a nuclear and cytoplasmic complex (C alpha) of identical mobility to Ca mainly consists of p50 and p75c-rel. While p50 and p65 levels do not change during pre-B to B-cell differentiation, p75c-rel is 5- to 6-fold more abundant in B cells compared to pre-B cells, a finding consistent with the switch in NF-kappa B subunit usage. During lipopolysaccharide-induced B-cell proliferation, transient up-regulation of both the nuclear p50 homodimer and p75c-rel containing complex is mirrored by a concurrent increase in c-rel and p105 but not p65 mRNA expression, a finding consistent with rel-NF-kappa B expression in B cells being controlled by an autoregulatory mechanism.
Grumont
R J
RJ
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Gerondakis
S
S
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis* / Q000737:chemistry* / Q000302:isolation & purification; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D020569:Proto-Oncogene Proteins c-rel; D011519:Proto-Oncogenes / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis
D008070:Lipopolysaccharides; D046911:Macromolecular Substances; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D014157:Transcription Factors