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 μs mRNA production and differentiation to high rate IgM secretion. Anti-μ added concomitantly with LPS at the start of culture has been demonstrated to inhibit the LPS-induced increase in us 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-μ is mediated by the abrogation of the up-regulation of transcription of the μ-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-μ. These results suggest that the effect of anti-μ 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.