Identification of a conserved lipopolysaccharide-plus-interleukin-4-responsive element located at the promoter of germ line epsilon transcripts.

Rothman P, Li SC, Gorham B, Glimcher L, Alt F, Boothby M
Mol Cell Biol. 1991 11 (11): 5551-61

PMID: 1922063 · PMCID: PMC361925 · DOI:10.1128/mcb.11.11.5551

Treatment of splenic B lymphocytes and certain B-lineage cell lines with the mitogen lipopolysaccharide (LPS) and the lymphokine interleukin-4 (IL-4) induces expression of germ line immunoglobulin C epsilon transcripts and class switching to the C epsilon gene. We show that LPS-plus-IL-4 induction of germ line epsilon transcripts (termed I epsilon transcripts) occurs at the transcriptional level in an Abelson murine leukemia virus-transformed pre-B-cell line. A 1.1-kb region of DNA surrounding the I epsilon promoter endows inducible transcription to a heterologous reporter gene stably transfected into these cells; such inducible expression depends on combined treatment with LPS and IL-4. Analyses of constructs transiently introduced into a B-cell lymphoma line demonstrated that LPS-plus-IL-4-inducible expression can be conferred by a 179-bp segment of DNA spanning the I epsilon transcriptional initiation site. Mutational analyses demonstrated that this expression depended on DNA sequences within a conserved region directly upstream from the I epsilon transcriptional initiation region. One nuclear protein that is constitutively expressed in normal B cells binds to the downstream end of the conserved sequence; its binding specificity correlates with the functional effect of several mutations. Two additional proteins, which are induced by IL-4 treatment of splenic B cells, bind to the transcription initiation sites of I epsilon. These proteins are indistinguishable in binding assays from proteins previously shown to bind an enhancer region of the class II major histocompatibility complex gene A alpha.

MeSH Terms (17)

Abelson murine leukemia virus Animals Base Sequence Cell Line Cell Line, Transformed Immunoglobulin Constant Regions Immunoglobulin epsilon-Chains Immunoglobulin Switch Region Interleukin-4 Lipopolysaccharides Lymphoma, B-Cell Mice Molecular Sequence Data Oligonucleotides Promoter Regions, Genetic Transcription, Genetic Transfection

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