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.
DOI of Published Version
Mol Cell Biol. 1998 Sep;18(9):5523-32.
Molecular and cellular biology
Lin SC, Wortis HH, Stavnezer J. (1998). The ability of CD40L, but not lipopolysaccharide, to initiate immunoglobulin switching to immunoglobulin G1 is explained by differential induction of NF-kappaB/Rel proteins. Women’s Health Research Faculty Publications. https://doi.org/10.1128/MCB.18.9.5523. Retrieved from https://escholarship.umassmed.edu/wfc_pp/200