Anti-CD23 monoclonal antibody inhibits germline Cε transcription in B cells

Yabuuchi, Shingo; Nakamura, Takehiko; Kloetzer, William S.; Reff, Mitchell E.

doi:10.1016/s1567-5769(01)00187-4

Cited by 24 publications

(22 citation statements)

References 36 publications

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“…CD23 binding appears to play a pivotal role in the inhibitory effect of GE2s, as might be predicted from studies with monoclonal anti-CD23 (21). Although how GE2 induces ERK phosphorylation is unknown, we found that it is also dependent on CD23 binding.…”

Section: Discussionsupporting

confidence: 70%

See 1 more Smart Citation

Inhibition of Interleukin-4-induced Class Switch Recombination by a Human Immunoglobulin Fcγ-Fcϵ Chimeric Protein

Yamada

Zhu²,

Zhang³

et al. 2003

Journal of Biological Chemistry

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Immunoglobulin E (IgE) is important in mediating human allergic diseases. We tested the hypothesis that a human Ig Fc␥-Fc⑀ bifunctional chimeric protein, GE2, would inhibit IgE class switch recombination (CSR) by co-aggregating B-cell CD32 and CD23. Indeed, GE2 directly inhibited ⑀ germ-line transcription, subsequent CSR to ⑀ and IgE protein production. This CSR inhibition was dependent on CD23 binding and the phosphorylation of extracellular signal-related kinase (ERK), and it was mediated via suppression of interleukin-4-induced STAT6 phosphorylation. Treatment with PD98059, a specific inhibitor of mitogen-activated protein kinase kinase 1 (MAPKK1 (MEK1)) and MEK2 reversed the ability of GE2 to decrease CSR and STAT6 phosphorylation. GE2 stimulation induced ERK phosphorylation, whereas it did not alter the phosphorylation of c-Jun N-terminal kinase or p38 MAPK. The ability of GE2 to block human isotype switching to ⑀, in addition to its already demonstrated ability to inhibit mast cell and basophil function, suggests that it will provide an important novel benefit in the treatment of IgE-mediated diseases.

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Section: Discussionsupporting

confidence: 70%

“…Anti-CD23 monoclonal antibody has been reported recently to inhibit ⑀ GT production in B cells (21). Because GE2 binds to CD23, we examined the ability of GE2 to alter IL-4-plus-CD40 induction of ⑀GT transcription.…”

Section: Inhibition Of S-s⑀ Recombination and Ige Production By Igmentioning

confidence: 99%

Inhibition of Interleukin-4-induced Class Switch Recombination by a Human Immunoglobulin Fcγ-Fcϵ Chimeric Protein

Yamada

Zhu²,

Zhang³

et al. 2003

Journal of Biological Chemistry

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“…First, as a control, we examined the antibody, lumiliximab, an anti-CD23 antibody produced as a potential therapy for allergic asthma. Results from in vitro studies clearly showed that lumiliximab blocked the production of IgE in human PBMC (37,38). To determine whether CD23 was involved in IgE synthesis in a purified B cell system, we investigated the outcome of blocking CD23 with lumiliximab.…”

Section: Kinetics Of Interaction Of Cd23 Fragments With C⑀2-4-mentioning

confidence: 99%

Soluble CD23 Monomers Inhibit and Oligomers Stimulate IGE Synthesis in Human B Cells

McCloskey

Hunt

Beavil

et al. 2007

Journal of Biological Chemistry

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The low affinity IgE receptor, CD23, is implicated in IgE regulation and the pathogenesis of allergic disease. CD23 is a type II integral membrane protein, comprising a lectin "head," N-terminal "stalk," and C-terminal "tail" in the extracellular sequence. Endogenous proteases cleave CD23 in the stalk and the tail to release soluble fragments that either stimulate or inhibit IgE synthesis in human B cells. The molecular basis of these paradoxical activities is not understood. We have characterized three fragments of CD23, monomeric derCD23, monomeric exCD23, and oligomeric lzCD23. We show that the monomers inhibit and the oligomer stimulates IgE synthesis in human B cells after heavy chain switching to IgE. CD23 fragments could be targets for therapeutic intervention in allergic disease.

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“…Sherr et al (17) were the first to demonstrate that anti-CD23 has the ability to inhibit IgE production, and a number of additional studies have confirmed this finding both in vivo and in vitro (18 -20). One of the most recent studies demonstrated that the ⑀ germline transcript is inhibited, suggesting that the mechanism involves inhibition of isotype switching (21). In contrast, Abs that bind the stalk promote an increase in IgE levels in vivo and in vitro (19,22).…”

mentioning

confidence: 99%

CD23 Trimers Are Preassociated on the Cell Surface Even in the Absence of Its Ligand, IgE

Kilmon

Shelburne

Chan‐Li

et al. 2004

The Journal of Immunology

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Allergic disease is mediated by high levels of allergen-specific IgE. IgE binding to CD23, the low affinity receptor for IgE, results in a negative feedback signal leading to a decrease in IgE production. Previous studies have shown that CD23 associates as an oligomer and that cooperative binding of at least two lectin domains is required for high affinity IgE binding to CD23. We have previously shown that cooperative binding is required for regulation of IgE production. This study describes the production of several mAbs that bind the stalk region of murine CD23. One of the Abs, 19G5, inhibited the IgE/CD23 interaction at 37°C, but not at 4°C. Analysis of the binding properties of these Abs revealed that CD23 dissociates at high temperatures, such as 37°C; however, the N terminus is constitutively associated, indicating partial, rather than complete, dissociation. A novel finding was that the stalk region, previously thought to mediate trimer association, was not required for oligomerization. These data reveal important information about the structure of CD23 that may be useful in modulating IgE production.

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Anti-CD23 monoclonal antibody inhibits germline Cε transcription in B cells

Cited by 24 publications

References 36 publications

Inhibition of Interleukin-4-induced Class Switch Recombination by a Human Immunoglobulin Fcγ-Fcϵ Chimeric Protein

Inhibition of Interleukin-4-induced Class Switch Recombination by a Human Immunoglobulin Fcγ-Fcϵ Chimeric Protein

Soluble CD23 Monomers Inhibit and Oligomers Stimulate IGE Synthesis in Human B Cells

CD23 Trimers Are Preassociated on the Cell Surface Even in the Absence of Its Ligand, IgE

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