THE SUBUNIT COMPOSITION OF NF-KAPPA-B COMPLEXES CHANGES DURING B-CELLDEVELOPMENT

The transcription factor NF-kappa B, shown to be essential for express ion of the immunoglobulin C kappa gene, is a key regulatory component in pre-B to B-cell differentiation. While previous studies have used l ymphoid cell line models, here we examine the expression and subunit c omposition of rel/NF-kappa B complexes in normal murine pre-B and B ly mphocytes. Two major NF-kappa B complexes are detected in pre-B and B cells. A high mobility complex, found in pre-B (C-b) and B cells (C be ta) 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 cy toplasmic complex (C alpha) of identical mobility to C-a mainly consis ts of p50 and p75(c-rel). While p50 and p65 levels do not change durin g pre-B to B-cell differentiation, p75(c-rel) is 5- to 6-fold more abu ndant in B cells compared to pre-B cells, a finding consistent with th e switch of NF-kappa B subunit usage. During lipopolysaccharide-induce d B-cell proliferation, transient up-regulation of both the nuclear p5 0 homodimer and p75(c-rel) containing complex is mirrored by a concurr ent 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.