CD40 and IgE: synergism between anti-CD40 monoclonal antibody and interleukin 4 in the induction of IgE synthesis by highly purified human B cells.

Jabara, Haifa H.; Fu, Shu Man; Geha, Raif S.; Vercelli, Donata

doi:10.1084/jem.172.6.1861

Cited by 429 publications

(197 citation statements)

References 19 publications

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“…Anti‐CD40 and IL‐4 stimulation induced an increase in total IgE levels in culture supernatants of both allergic subjects as previously described30, 31 (Fig. S2).…”

Section: Resultssupporting

confidence: 62%

“…This hypothesis has been controversially discussed with arguments in favour14, 16, 32, 33 and against34, 35 the potential of omalizumab to activate IgE + memory B cells. In the present study, both in our in vivo intranasal challenge model and in our in vitro approach using a well‐established system to induce IgE production,30, 31 we did not observe any enhancing effect of omalizumab on IgE production. Results from the in vitro experiments indicate that omalizumab is not able to activate IgE‐producing cells by cross‐linking of the IgE‐BCR.…”

Section: Discussioncontrasting

confidence: 46%

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Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels—A pilot study

Eckl‐Dorna

Fröschl

Lupinek

et al. 2017

Allergy

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BackgroundAdministration of the therapeutic anti‐IgE antibody omalizumab to patients induces strong increases in IgE antibody levels.ObjectiveTo investigate the effect of intranasal administration of major birch pollen allergen Bet v 1, omalizumab or placebo on the levels of total and allergen‐specific IgE in patients with birch pollen allergy.MethodsBased on the fact that intranasal allergen application induces rises of systemic allergen‐specific IgE, we performed a double‐blind placebo‐controlled pilot trial in which birch pollen allergic subjects were challenged intranasally with omalizumab, placebo or birch pollen allergen Bet v 1. Total and allergen‐specific IgE, IgG and basophil sensitivity were measured before and 8 weeks after challenge. For control purposes, total, allergen‐specific IgE levels and omalizumab‐IgE complexes as well as specific IgG levels were studied in subjects treated subcutaneously with either omalizumab or placebo. Effects of omalizumab on IgE production by IL‐4/anti‐CD40‐treated PBMCs from allergic patients were studied in vitro.ResultsIntranasal challenge with Bet v 1 induced increases in Bet v 1‐specific IgE levels by a median of 59.2%, and this change differed significantly from the other treatment groups (P = .016). No relevant change in allergen‐specific and total IgE levels was observed in subjects challenged with omalizumab. Addition of omalizumab did not enhance IL‐4/anti‐CD40‐induced IgE production in vitro. Significant rises in total IgE (mean IgE before: 131.83 kU/L to mean IgE after: 505.23 kU/L) and the presence of IgE‐omalizumab complexes were observed after subcutaneous administration of omalizumab.ConclusionIntranasal administration of allergen induced rises of allergen‐specific IgE levels, whereas intranasal administration of omalizumab did not enhance systemic total or allergen‐specific IgE levels.

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“…Anti‐CD40 and IL‐4 stimulation induced an increase in total IgE levels in culture supernatants of both allergic subjects as previously described30, 31 (Fig. S2).…”

Section: Resultssupporting

confidence: 62%

Section: Discussioncontrasting

confidence: 46%

Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels—A pilot study

Eckl‐Dorna

Fröschl

Lupinek

et al. 2017

Allergy

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“…IL-4 also stimulates the expression of AID (16). A further requirement for CSR in primary B cells is CD40 signaling (12,17). Allergen stimulates the expression of IL-4 and CD40 ligand by Th2 cells and mast cells in the nasal mucosa in allergic rhinitis (18,19).…”

mentioning

confidence: 99%

“…IL-4 stimulates the transcription of all the germline genes and is necessary for stimulation of the ⑀ germline gene (12)(13)(14)(15). IL-4 also stimulates the expression of AID (16).…”

mentioning

confidence: 99%

Allergen Drives Class Switching to IgE in the Nasal Mucosa in Allergic Rhinitis

Takhar

Smurthwaite

Coker

et al. 2005

The Journal of Immunology

198

187

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IgE-expressing B cells are over 1000 times more frequent in the nasal B cell than the peripheral blood B cell population. We have investigated the provenance of these B cells in the nasal mucosa in allergic rhinitis. It is generally accepted that expression of activation-induced cytidine deaminase and class switch recombination (CSR) occur in lymphoid tissue, implying that IgE-committed B cells must migrate through the circulation to the nasal mucosa. Our detection of mRNA for activation-induced cytidine, multiple germline gene transcripts, and ε circle transcripts in the nasal mucosa of allergic, in contrast to nonallergic control subjects, however, indicates that local CSR occurs in allergic rhinitis. The germline gene transcripts and ε circle transcripts in grass pollen-allergic subjects are up-regulated during the season and also when biopsies from allergic subjects are incubated with the allergen ex vivo. These results demonstrate that allergen stimulates local CSR to IgE, revealing a potential target for topical therapies in allergic rhinitis.

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“…Differentiation of B cells to IgE-producing plasma cells requires two distinct signals, the first provided by IL-4 and IL-13 (19,20), the second by interaction between the co-stimulatory antigen CD40 on the surface of B cells with CD40-ligand on T-cell surfaces (21,22).…”

mentioning

confidence: 99%