The ability of CD40L, but not lipopolysaccharide, to initiate immunoglobulin switching to immunoglobulin G1 is explained by differential induction of NF-kappaB/Rel proteins
Department of Molecular Genetics and Microbiology
Animals; Antigens, CD40; B-Lymphocytes; CD40 Ligand; Chloramphenicol O-Acetyltransferase; Genes, Reporter; Immunoglobulin Class Switching; Immunoglobulin G; Interleukin-4; Lipopolysaccharides; Luciferases; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; NF-kappa B; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-rel; Recombinant Fusion Proteins; Spleen; T-Lymphocytes; Transcription Factors; Transcription, Genetic; Transfection
Life Sciences | Medicine and Health Sciences | Women's Studies
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-kappaB/Rel to induce germ line gamma1 transcripts, which are essential for class switch recombination. Although LPS also activates NF-kappaB, it poorly induces germ line gamma1 transcripts. Western blot analyses show that CD40 ligand (CD40L) induces all NF-kappaB/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-kappaB complexes binding to the germ line gamma1 promoter, whereas in LPS-treated cells, p50-c-Rel and p50-p50 dimers are the major binding complexes. Transfection of expression plasmids for NF-kappaB/Rel fusion proteins (forced dimers) indicates that p50-RelA and p50-RelB dimers activate the germ line gamma1 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 gamma1 transcription depends on the composition of NF-kappaB/Rel proteins.
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Citation: Mol Cell Biol. 1998 Sep;18(9):5523-32.
Lin, S. C.; Wortis, H. H.; and Stavnezer, Janet, "The ability of CD40L, but not lipopolysaccharide, to initiate immunoglobulin switching to immunoglobulin G1 is explained by differential induction of NF-kappaB/Rel proteins" (1998). Women’s Health Research Faculty Publications. Paper 200.