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 polype ptides is thought to function both as a developmental regulator in B c ells and as a rapid response system in all cells. To examine this noti on in more detail, we determined the protein contents of both the indu cible 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 my ristate acetate treatment of 70Z/3 cells. The constitutive and inducib le complexes in WEHI 231 cells are mainly composed of p50 and Rel. The constitutive or induced activities are all sensitive to I kappa B-alp ha, but this inhibitor is very short-lived in WEHI 231 cells, suggesti ng that the balance between synthesis and degradation of I kappa B-alp ha determines whether a particular cell lineage has constitutive activ ity. A patterned expression of the NF-kappa B/Rel activator proteins e merges from an analysis of other B-lineage cell lines and splenic B ce lls: 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 plasm acytoma lines, This ordered pattern of regulators may reflect the requ irement for expression of different genes during terminal B-cell diffe rentiation because different combinations of NF-kappa B/Rel family mem bers preferentially activate distinct KB sites in reporter constructs.