Sequential induction of NF-κB/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.
© 1994 by the American Society for Microbiology. Received 22 March 1994/Returned for modification 25 April 1994/Accepted 6 May 1994. We thank R. Bravo, R. Dalla-Favera, N. Rice, and C.-C. Chang for the antisera against RelB and p52 proteins, and we thank L. Glimcher for M12 and p3X63Ag cell lines. We thank A. Czernik and P. Greengard for technical advice and facility on the phosphopeptide analyses. We also thank A. Beg, C. Roman, and Z.-S. Ye for critical comments on the manuscript. H.-C.L. is a Fellow of the Cancer Research Institute. W.S. is supported by a fellowship from NIH grant AI08724-02. This work, H.-C.L., and M.L.S. are supported by grants CA51462 and GM39458 to D.B.
Published - LIOmcb94.pdf