Transcriptional analysis of inhibition of lipopolysaccharide response by anti-IgM.
Murine splenic B cells, when stimulated with LPS, show a generalized enhancement of gene transcription. In addition to this general increase, there is a specific increase in microseconds mRNA production and differentiation to high rate IgM secretion. Anti-mu added concomitantly with LPS at the start of culture has been demonstrated to inhibit the LPS-induced increase in microseconds mRNA production without affecting the proliferative capacity of the cells. By "run-on" analysis of nascent transcription, we have shown that the effect of anti-mu is mediated by the abrogation of the up-regulation of transcription of the mu-gene induced by LPS. Furthermore, by assessing the site of transcription termination, it is possible to infer that alterations in 3'-end processing induced by LPS are also inhibited. We have also found that CAT3 gene activity driven by a number of promoter/enhancers with diverse regulatory motifs are inhibited by anti-mu. These results suggest that the effect of anti-mu cannot be restricted to interactions with a single regulatory element. Therefore, cross-linking of surface IgM may affect a number of genes involved in differentiation to Ig secretion.
Moore
B B
BB
University of Texas Southwestern Medical Center, Immunology Graduate Program, Dallas 75235.
Ariizumi
K
K
Tucker
P W
PW
Yuan
D
D
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis / Q000235:genetics; D005260:Female; D007075:Immunoglobulin M / Q000276:immunology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D014158:Transcription, Genetic; D014162:Transfection
D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; C044203:anti-IgM; D015500:Chloramphenicol O-Acetyltransferase