Structure and expression of germline epsilon transcripts in human B cells induced by interleukin 4 to switch to IgE production.

Gauchat, J F; Lebman, Deborah A.; Coffman, Robert L.; Gascan, Hugues; Vries, J E de

doi:10.1084/jem.172.2.463

Cited by 326 publications

(181 citation statements)

References 58 publications

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“…Therefore, the mouse and human GL ⑀ promoters are probably not regulated identically. For example, induction of GL ⑀ transcripts in mouse splenic B cells requires IL-4 plus CD40L or LPS, whereas induction of GL ⑀ transcripts in human peripheral blood B cells requires only IL-4, although the response can be further enhanced by some NF-B inducers (6). In this study, we found AP-1 activity is induced in mouse splenic B cells by CD40L, but we could not detect C/EBP␤ in nuclear extracts from cells either untreated or treated with CD40L for 4 h by Western blotting (data not shown).…”

Section: Regulation Of Ig Gl ⑀ Transcripts Differs Between Mouse and mentioning

confidence: 99%

“…(6,16). The divergent binding sites for AP-1 in mouse and C/EBP in human are boxed separately, whereas the conserved binding sites for Stat6 (16,19), NF-B (12,16,19), and BSAP (58) Therefore, transient induction of AP-1 and NF-B might be sufficient to support activation of the GL ⑀ promoter by Stat6.…”

Section: Kinetics Of Induction and Half-life Of Gl ⑀ Transcripts In Mmentioning

confidence: 99%

“…The transcripts initiate at a 5Ј-exon (or I exon) and are transcribed through the switch region, terminating at the 3Ј-end of the C H gene. After splicing, the germline transcripts contain the I exon and the exons of the C H gene, deleting the switch region sequences and introns of the C H gene (1,2,5,6).…”

mentioning

confidence: 99%

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Activation of the Mouse Ig Germline ε Promoter by IL-4 Is Dependent on AP-1 Transcription Factors

Shen

Stavnezer

2001

The Journal of Immunology

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Induction of germline (GL) ε transcripts, an essential step preceding Ig isotype switching to IgE, requires activation of transcription factors by IL-4 and a B cell activator, e.g., CD40 ligand or LPS. We demonstrate that AP-1 (Fos and Jun), induced transiently by CD40 ligand or LPS, binds a DNA element in the mouse GL ε promoter. AP-1 synergizes with Stat6 to activate both the intact GL ε promoter and a minimal heterologous promoter driven by the AP-1 and Stat6 sites of the mouse GL ε promoter. By contrast, C/EBPβ, which trans-activates the human GL ε promoter, inhibits IL-4 induction of the mouse promoter, probably by attenuating the synergistic interaction between AP-1 and Stat6. Furthermore, AP-1 does not trans-activate the human GL ε promoter. Thus, induction of GL ε transcripts in mice and humans may be regulated differently. In addition, although mouse GL ε transcripts have a half-life of ∼100 min, the RNA level continues to increase for up to 24 h, and the promoter appears to be active for at least 2 days after B cell activation. Altogether, these data suggest that induction of AP-1 activity, although transient, is required for activation of the mouse GL ε promoter by IL-4-induced Stat6.

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Section: Regulation Of Ig Gl ⑀ Transcripts Differs Between Mouse and mentioning

confidence: 99%

Section: Kinetics Of Induction and Half-life Of Gl ⑀ Transcripts In Mmentioning

confidence: 99%

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Activation of the Mouse Ig Germline ε Promoter by IL-4 Is Dependent on AP-1 Transcription Factors

Shen

Stavnezer

2001

The Journal of Immunology

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“…The first is delivered by specific cytokines that activate the promoter of the relevant immunoglobulin isotype 22 and the second by CD40L expressed on the CD4 T cells. 23 IL-4 was shown 24 to switch B cells to IgE and subsequently interferon-c was identified as the switch factor for IgG1 in humans 25 and IgG2a in the mouse.…”

Section: How Is Ige Class Switching Controlled?mentioning

confidence: 99%

The role of the T follicular helper cells in allergic disease

Kemeny

2012

Cell Mol Immunol

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DM KemenyT follicular helper (Tfh) cells were discovered just over a decade ago as germinal centre T cells that help B cells make antibodies. Included in this role is affinity maturation and isotype switching. It is here that their functions become less clear. Tfh cells principally produce IL-21 which inhibits class switching to IgE. Recent studies have questioned whether the germinal centre is the main site of IgE class switching or IgE affinity maturation. In this review, I will examine the evidence that these cells are responsible for regulating IgE class switching and the relationship between Tfh cells and T helper 2 (Th2) effector cells.

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“…Stimulation of B cells with IL-4 alone induces the expression of germ-line Cf transcripts [8]. The additional signal is required to further induce class switching to IgE, which results in the accumulation of mature (membrane-bound and productive) Cf transcripts leading lo Correspondence: Yukiyoshi Yaoagihara, Clinical Research Centre Ibr Allergy.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of IL-4 receptor up-regulation on B cells by antisense oligodeoxynucleotide suppresses IL-4-induced human IgE production

Ikizawa

Kondo

Koshio

et al. 1995

Clinical and Experimental Immunology

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SUMMARYlL-4 is shown to up-regulate its own receptor (IL-4R) on human lymphocytes, but the functional significance of up-regulated IL-4R is not clear regarding IgE production. This study investigated the possible role of IL-4-induced up-regulation of IL-4R on B cells in the induction ofhuman IgE synthesis by means of antisense strategy. Among three antisense oligodeoxynucleotides designed against the downstream of translation initiation siteof 1L-4R cDNA. S-oligo [.complementary to nucleotide 1-24, showed the strongest inhibition ofthe constitutive expression of IL-4R on Daudi cells. Addition of S-oligo ! together with IL-4 also decreased the up-regulated but not constitutive levels of IL-4R on peripheral blood B cells without affecting the concomitant enhancement of CD23, CD40, HLA-DR and surface IgM expression, indicating that ils effect is specific for IL-4R up-regulation. When S-oligo 1 was added to B cells costimulated with IL-4 and anti-CD40 MoAb, it induced a dose-dependent inhibition of IgE production. This inhibition was accompanied by a decrease in the expression of mature C< transcripts, whereas the accumulation of germ-line O transcripts was not affected by S-oligo 1. These data suggest that the signal transduclion mediated by the up-regulated IL-4R on B cells may be intimately associated with the induction of isotype switching to IgE thai leads to mature Ce transcription and IgE production.

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Structure and expression of germline epsilon transcripts in human B cells induced by interleukin 4 to switch to IgE production.

Cited by 326 publications

References 58 publications

Activation of the Mouse Ig Germline ε Promoter by IL-4 Is Dependent on AP-1 Transcription Factors

Activation of the Mouse Ig Germline ε Promoter by IL-4 Is Dependent on AP-1 Transcription Factors

The role of the T follicular helper cells in allergic disease

Inhibition of IL-4 receptor up-regulation on B cells by antisense oligodeoxynucleotide suppresses IL-4-induced human IgE production

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