In vitro IgE inhibition in B cells by anti-CD23 monoclonal antibodies is functionally dependent on the immunoglobulin Fc domain

Nakamura, Takehiko; Kloetzer, William S.; Brams, Peter; Hariharan, Kandasamy; Chamat, Soulaïma; Cao, Xiaojuan; LaBarre, Michael J.; Chinn, Paul; Morena, Ron A.; Shestowsky, William S.; Li, Yan Ping; Chen, Agnes; Reff, Mitchell E.

doi:10.1016/s0192-0561(99)00068-5

Cited by 46 publications

(35 citation statements)

References 35 publications

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“…These findings are consistent with its published expression in the epithelium and increased gene transcription in peribronchial and perivascular inflammatory cells in an allergen induced murine model of asthma [5]. ADAM8 can cleave CD23, the low-affinity IgE receptor (FcεRIIb) [25], which is involved in up regulation of IL-4 induced synthesis of IgE in B-cells [26]. CD23 shedding would counteract IgE-mediated immune responses, next to inducing release of proinflammatory mediators from macrophages [27].…”

Section: Discussionsupporting

confidence: 70%

Expression of ADAMs (“a disintegrin and metalloprotease”) in the human lung

et al. 2009

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In view of the associations of "a disintegrin and metalloprotease" (ADAM) with respiratory diseases, we assessed the expression of various ADAMs in human lung tissue. Lung tissue was obtained from nine individuals who underwent surgery for lung cancer or underwent lung transplantation for emphysema. Also, 16HBE 14o-(human bronchial epithelial) and A549 (alveolar type II epitheliumlike) cell lines were used. Immunohistochemistry was performed with antibodies recognizing different ADAM domains. The ADAMs were typically distributed over the bronchial epithelium. ADAM8 and ADAM10 were expressed diffusely in all layers of the epithelium. ADAM9, ADAM17, and ADAM19 were predominantly expressed in the apical part of the epithelium, and ADAM33 was predominantly and strongly expressed in basal epithelial cells. In smooth muscle, ADAM19 and ADAM17 were strongly expressed, as was ADAM33, though this expression was weaker. ADAM33 was strongly expressed in vascular endothelium. All ADAMs were generally expressed in inflammatory cells. The typical distribution of ADAMs in the lung, especially in the epithelium, is interesting and suggests a localized function. As most ADAMs are involved in release of (pro-) inflammatory mediators and growth factors, they may play an important role in the first line of defense and in initiation of repair events in the airways.

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Section: Discussionsupporting

confidence: 70%

Expression of ADAMs (“a disintegrin and metalloprotease”) in the human lung

et al. 2009

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“…Nakamura et al (5) found that the inhibitory effect of ␣CD23 on human IgE production is dependent on the Fc␥ domain and GE2 is expected to function through Fc␥R binding. However, the role(s) of Fc␥RIIA versus -B in the effects of GE2 will require further dissection.…”

Section: Discussionmentioning

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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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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“…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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In vitro IgE inhibition in B cells by anti-CD23 monoclonal antibodies is functionally dependent on the immunoglobulin Fc domain

Cited by 46 publications

References 35 publications

Expression of ADAMs (“a disintegrin and metalloprotease”) in the human lung

Expression of ADAMs (“a disintegrin and metalloprotease”) in the human lung

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

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