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Molecular and Cellular Biology, September 1998, p. 5523-5532, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Ability of CD40L, but Not Lipopolysaccharide, To Initiate Immunoglobulin Switching to Immunoglobulin G1 Is Explained by Differential Induction of NF-kappa B/Rel Proteins

Shih-Chang Lin,1 Henry H. Wortis,2 and Janet Stavnezer1,*

Department of Molecular Genetics and Microbiology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0122,1 and Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111-18002

Received 14 November 1997/Returned for modification 13 January 1998/Accepted 25 June 1998

Antibodies of the immunoglobulin G1 class are induced in mice by T-cell-dependent antigens but not by lipopolysaccharide (LPS). CD40 engagement contributes to this preferential isotype production by activating NF-kappa B/Rel to induce germ line gamma 1 transcripts, which are essential for class switch recombination. Although LPS also activates NF-kappa B, it poorly induces germ line gamma 1 transcripts. Western blot analyses show that CD40 ligand (CD40L) induces all NF-kappa B/Rel proteins, whereas LPS activates predominantly p50 and c-Rel. Electrophoretic mobility shift assays show that in CD40L-treated cells, p50-RelA and p50-RelB dimers are the major NF-kappa B complexes binding to the germ line gamma 1 promoter, whereas in LPS-treated cells, p50-c-Rel and p50-p50 dimers are the major binding complexes. Transfection of expression plasmids for NF-kappa B/Rel fusion proteins (forced dimers) indicates that p50-RelA and p50-RelB dimers activate the germ line gamma 1 promoter and that p50-c-Rel and p50-p50 dimers inhibit this activation by competitively binding to the promoter without activating the promoter. Therefore, germ line gamma 1 transcription depends on the composition of NF-kappa B/Rel proteins.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology and Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA 01655-0122. Phone: (508) 856-4100. Fax: (508) 856-1789. E-mail: janet.stavnezer{at}banyan.ummed.edu.

Molecular and Cellular Biology, September 1998, p. 5523-5532, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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