In vivo murine CD23 destabilization enhances CD23 shedding and IgE synthesis

Ford, Jill; Kilmon, Michelle A.; Haas, Karen M.; Shelburne, Anne E.; Chan‐Li, Yee; Conrad, Daniel H.

doi:10.1016/j.cellimm.2007.01.004

Cited by 24 publications

(22 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As shown in Fig. 2A, the enhanced CD23 cleavage that is characteristic of the anti-stalk mAb, 19G5 (8), is reversed in the presence of 10 mM NH 4 Cl. In contrast, NH 4 Cl treatment of mCD23 ϩ -CHO where CD23 was stabilized with monomeric IgE had no affect with respect to sCD23 production (Fig.…”

Section: Resultsmentioning

confidence: 72%

“…To determine whether there was a correlation between CD23 cleavage and internalization, 293T cells were transfected with CD23-YFP. Previous studies had shown that stabilizing CD23 with IgE or anti-lectin antibodies decreased CD23 cleavage, whereas destabilizing antibodies increased cleavage (8,12). The CD23-YFP expressing 293T cells were then incubated with the indicated antibodies for 24 h and examined by immunofluorescence.…”

Section: Resultsmentioning

confidence: 99%

“…7). Because CD23 cleavage enhances IgE production (8) and given the IgE regulation seen with the intact molecule, blocking cleavage of CD23 represents a potential way to inhibit IgE synthesis and ultimately, type I allergic disease. Soluble CD23 (sCD23) retains IgE-binding ability, although at much lower affinity/avidity than membrane trimeric CD23.…”

mentioning

confidence: 99%

“…IgE (11) and monoclonal anti-CD23 that are directed against the lectin domain (12) both protect CD23 from cleavage and thus, decrease IgE production; these reagents are termed CD23 stabilizing antibodies. Monoclonal antibodies that are directed against the stalk region of CD23 have been shown in both human (12) and mouse (8) to enhance CD23 cleavage, as well as enhance IgE production. As such, they are called CD23 destabilizing antibodies.…”

mentioning

confidence: 99%

See 3 more Smart Citations

CD23 Sheddase A Disintegrin and Metalloproteinase 10 (ADAM10) Is Also Required for CD23 Sorting into B Cell-derived Exosomes

Mathews

Gibb

Chen

et al. 2010

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The low affinity receptor for IgE, CD23, is the natural regulator of IgE synthesis, and understanding both the synthesis and the catabolism of CD23 are, thus, important issues. Membrane CD23 is cleaved by a disintegrin and metalloproteinase 10 (ADAM10) and this cleavage influences the ability of CD23 to regulate IgE. In contrast to the belief that cleavage is a cell surface event, endosomal neutralization with NH 4 Cl was found to dramatically reduce CD23 cleavage, suggesting that the majority of CD23 cleavage occurred subsequent to internalization in the endosomal pathway and not at the cell surface. In line with this, full-length CD23 was shown to be sorted in an ADAM10-dependent manner into exosomes. Greatly increased ADAM10-mediated CD23 cleavage was seen at endosomal pH. Additionally, the stalk region of CD23 was found to interact with ADAM10 and ADAM10 binding of CD23 was found to be protease independent. SPR analysis of the interaction indicated about a 10-fold increase in the R max at endosomal pH (pH 5.8) compared with pH 7.4, whereas the affinity of the interaction was not significantly changed. The R max change, combined with the increased cleavage at endosomal pH, indicates greater accessibility of the CD23 stalk region for ADAM10 at the lower pH. These results indicate a model where CD23 internalization results in ADAM10-dependent incorporation into exosomes, followed by partial cleavage of CD23 by ADAM10 prior to being released from the cell. The increased cleavage at endosomal pH also has implications for other ADAM10 substrates.The cleavage of plasma membrane-bound proteins and their subsequent release from the cell is described as ectodomain shedding. Historically this was believed to be a cell surface process. However, recently a second mechanism was discovered, involving the release of proteins after their internalization and subsequent trafficking through the endosomal pathway to multivesicular bodies (MVB) 2 (1). In the MVB, the proteins can interact with their sheddase and be cleaved and released or be sorted into exosomes and released as full-length proteins. Exosomes are small, 30 -100 nm, membrane containing vesicles that are released by a wide variety of cells. As they have high expression of major histocompatibility complexes (MHC) molecules they have been investigated as cell-free transporters of cancer antigens in cancer immunotherapy treatments (2). Exosome released from B cells have also been extensively studied. B cell-derived exosomes express integrins (3), which allow them to bind, and potentially present antigen to T cells. They also transport antigens, including peptides derived from allergen between antigen presenting cells (reviewed in Ref. 4). B cell exosome secretion is also increased upon activation (5) and interaction with T cells (6). However, the secretion of exosomes by cells as well as the mechanism that controls the sorting of proteins into exosomes are still poorly understood. The low-affinity receptor of immunoglobulin E (CD23) is an important regulator of IgE pro...

show abstract

Section: Resultsmentioning

confidence: 72%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

CD23 Sheddase A Disintegrin and Metalloproteinase 10 (ADAM10) Is Also Required for CD23 Sorting into B Cell-derived Exosomes

Mathews

Gibb

Chen

et al. 2010

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, it is important to better define the identities of the CD8 ϩ CD60 ϩ T cell subset (CD23 ϩ/Ϫ ) that help and/or suppress memory IgE responses in order that cells/ cytokine pathways might be accurately determined. Because CD23 is shed from cell surfaces (11)(12)(13) ϩ T cells; other cytokines were not studied). Interestingly, in the present studies, IL-13 was not required for induction of memory IgE responses.…”

Section: Discussionmentioning

confidence: 99%

Two Distinct T Cell Subsets, CD4+ and CD8+CD60+, and Their Cytokines Are Required for In Vitro Induction of Human Ragweed-Specific Memory IgE Responses

Smith‐Norowitz

Silverberg

Norowitz

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

CD8+CD60+ T cells (80–98% CD45RO+; 20% CD23+) are significantly increased in the blood of serum IgE+ ragweed-sensitized (RS) compared with serum IgE-nonatopic humans (p = 0.001). CD8+CD60+ T cells of the RS patients produced IL-2, IL-4, IL-10, IL-12, IFN-α. and IFN-γ, but not IL-6 or IL-13. When their PBMC were cultured with ragweed Ag (RA), peak IgE responses occurred on day 10; none was induced with non-cross-reacting or without Ag; nonatopic PBMC did not respond to any stimulant. When either CD4+ or CD8+CD60+ T cells were depleted from RS PBMC before culture with RA, no IgE responses were induced. If purified CD4+ T cells or low numbers of CD8+CD60+ T cells were added back to the depleted PBMC, IgE responses were restored. However, higher numbers of CD8+CD60+ T cells totally suppressed IgE responses. Total suppression also was obtained when RS PBMC were cultured with RA and either anti-IL-2, IL-4, IL-10, IL-12, IFN-γ (all concentrations), or IFN-α (low concentrations), but not anti-IL-6 or IL-13. Higher concentrations of anti-IFN-α potentiated IgE responses.

show abstract

The Biology of IgE: Molecular Mechanism Restraining Potentially Dangerous High Serum IgE Titres In Vivo

et al. 2009

View full text Add to dashboard Cite

In vivo murine CD23 destabilization enhances CD23 shedding and IgE synthesis

Cited by 24 publications

References 49 publications

CD23 Sheddase A Disintegrin and Metalloproteinase 10 (ADAM10) Is Also Required for CD23 Sorting into B Cell-derived Exosomes

CD23 Sheddase A Disintegrin and Metalloproteinase 10 (ADAM10) Is Also Required for CD23 Sorting into B Cell-derived Exosomes

Two Distinct T Cell Subsets, CD4+ and CD8+CD60+, and Their Cytokines Are Required for In Vitro Induction of Human Ragweed-Specific Memory IgE Responses

The Biology of IgE: Molecular Mechanism Restraining Potentially Dangerous High Serum IgE Titres In Vivo

Contact Info

Product

Resources

About