GO:0019769 low-affinity IgE receptor activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0019769 low-affinity IgE receptor activity is a molecular function defined as binding IgE via its Fc region with low affinity and transmitting a signal across the membrane to change cell activity.
• The prototypical low-affinity IgE receptor is CD23 (FcεRII), a C-type lectin that exists as membrane-bound and soluble forms and performs multiple immune functions.
• CD23 is cleaved by the metalloproteinase ADAM10, releasing soluble CD23 fragments that retain IgE-binding capacity and can modulate immune responses.
• Low-affinity IgE receptor activity is implicated in allergic diseases such as atopic dermatitis, where CD23 regulation is altered.
• CD23-dependent mechanisms can also influence T and B cell alloresponses, linking this receptor to transplantation immunology.
• Research on GO:0019769 uses molecular, cellular, and genetic approaches including CRISPR knockout, point mutation, knock-in, and overexpression models to dissect CD23 function.
Description
The low-affinity IgE receptor activity (GO:0019769) is a molecular function that enables a cell to bind immunoglobulin E (IgE) with low affinity via the Fc region and transmit a signal across the membrane, thereby initiating a change in cell activity. This function is distinct from the high-affinity IgE receptor (FcεRI) and is primarily associated with CD23 (FcεRII), a type II membrane protein belonging to the C-type lectin family. CD23 is expressed on B cells, activated T cells, monocytes, and other cell types, and it plays a key role in IgE homeostasis and immune regulation. The importance of GO:0019769 lies in its involvement in allergic inflammation, host defense, and immune cell crosstalk. Understanding this function at the molecular level is essential for developing therapeutic strategies targeting IgE-mediated diseases.
low-affinity IgE receptor activity At A Glance
| GO ID | GO:0019769 |
|---|---|
| GO term | low-affinity IgE receptor activity |
| Ontology | molecular_function |
| Synonym | low affinity Fc receptor activity; low affinity IgE receptor activity |
| Major function | Binding IgE via Fc region with low affinity and transmitting a signal to change cell activity |
| Primary receptor | CD23 (FcεRII), a C-type lectin |
| Soluble form | Soluble CD23 fragments generated by proteolytic cleavage |
| Key protease | ADAM10 |
| Associated diseases | Atopic dermatitis, allergic inflammation, transplantation alloresponses |
What Is GO:0019769?
According to the Gene Ontology, GO:0019769 low-affinity IgE receptor activity is defined as combining with low affinity with an immunoglobulin of the IgE isotype via the Fc region, and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. In simpler terms, it is the ability of a cell surface receptor to grab IgE antibodies weakly and convert that binding into an intracellular signal that alters what the cell does.
Why Is low-affinity IgE receptor activity Important in Cell Biology?
GO:0019769 low-affinity IgE receptor activity is critical for understanding how IgE antibodies modulate immune cell behavior beyond classical high-affinity receptor pathways. CD23, the main low-affinity IgE receptor, regulates IgE synthesis, antigen presentation, and cell survival, and its dysregulation is linked to allergic diseases such as atopic dermatitis. Moreover, CD23-dependent mechanisms can amplify T and B cell alloresponses, highlighting its broader role in transplantation and immune tolerance. Targeting this activity may offer therapeutic avenues for allergic and immune-mediated disorders.
• Regulates IgE homeostasis and allergic sensitization.
• Expressed on B cells, activated T cells, monocytes, and eosinophils.
• Soluble CD23 fragments can act as cytokines or IgE-binding factors.
• Involved in antigen presentation and T cell activation.
• Implicated in atopic dermatitis pathogenesis.
• Modulates T and B cell alloresponses in transplantation.
• Target for anti-allergy therapies, e.g., anti-CD23 antibodies.
• Cleaved by ADAM10, linking to metalloproteinase regulation.
• Contributes to non-IgE-mediated anaphylaxis mechanisms.
• Provides a model for studying low-affinity receptor signaling.
Molecular Mechanism of low-affinity IgE receptor activity
IgE Binding and Receptor Oligomerization
In simple terms: The receptor grabs IgE weakly and clusters together to start signaling.
CD23 binds IgE via its C-type lectin domain with low affinity, and this interaction can lead to receptor oligomerization and signaling. The low-affinity nature allows rapid dissociation and fine-tuning of immune responses.
Proteolytic Cleavage by ADAM10
In simple terms: A scissor enzyme cuts the receptor, releasing a soluble piece that can still bind IgE.
The metalloproteinase ADAM10 cleaves membrane-bound CD23, releasing soluble CD23 fragments that retain IgE-binding capacity and can modulate immune cell functions. This cleavage is a key regulatory step in low-affinity IgE receptor activity.
Signal Transduction and Cellular Responses
In simple terms: Binding IgE triggers signals inside the cell that change its behavior.
Upon IgE binding, CD23 can transmit signals that regulate B cell survival, IgE synthesis, and cytokine release. The signaling pathways may involve interactions with other membrane proteins and kinases, though details remain to be fully elucidated.
Regulation by Soluble CD23
In simple terms: The soluble form of the receptor can act as a messenger to control immune responses.
Soluble CD23 fragments can bind IgE and modulate IgE synthesis, acting as positive or negative regulators depending on context. This adds a layer of complexity to low-affinity IgE receptor activity.
Key Genes Involved in GO:0019769 low-affinity IgE receptor activity
The following genes and proteins are central to low-affinity IgE receptor activity (GO:0019769) and its regulation.
| Gene | Major Role | Research Relevance |
|---|---|---|
| FCER2 (CD23) | Encodes the low-affinity IgE receptor | Primary gene for GO:0019769; target for knockout and knock-in studies |
| ADAM10 | Metalloproteinase that cleaves CD23 | Regulates soluble CD23 release; knockout reduces CD23 shedding |
| IGHE | Encodes IgE heavy chain | Ligand for CD23; mutations affect binding |
| FCER1A | High-affinity IgE receptor alpha chain | Contrasts with low-affinity receptor; co-expression studies |
| SPI1 (PU.1) | Transcription factor regulating FCER2 | Controls CD23 expression in B cells |
| STAT6 | Transcription factor in IL-4 signaling | Induces CD23 expression |
| IL4 | Cytokine inducing CD23 | Upregulates FCER2; used in overexpression models |
| IL13 | Cytokine inducing CD23 | Similar to IL-4; relevant in allergy |
| CD40 | Costimulatory molecule on B cells | Cooperates with CD23 in B cell activation |
| CD21 | Complement receptor 2 | Interacts with CD23 on B cells |
| ITAM-containing adaptors | Signaling molecules | May mediate CD23 signaling |
| SYK | Tyrosine kinase | Potential downstream of CD23 signaling |
| LYN | Src-family kinase | May regulate CD23 signaling |
| PI3K | Phosphoinositide 3-kinase | Possible pathway in CD23-mediated survival |
| NF-κB | Transcription factor | Activated downstream of CD23 in some contexts |
| ADAM17 | Related metalloproteinase | May also cleave CD23 in some cells |
| GATA2 | Transcription factor | Regulates CD23 in eosinophils |
| RUNX1 | Transcription factor | Involved in CD23 expression |
How Is low-affinity IgE receptor activity Regulated?
Low-affinity IgE receptor activity is regulated at multiple levels. Expression of FCER2 (CD23) is induced by cytokines such as IL-4 and IL-13 via STAT6 signaling. Proteolytic cleavage by ADAM10 controls the balance between membrane-bound and soluble CD23, thereby modulating receptor activity. Additionally, soluble CD23 fragments can feedback to regulate IgE synthesis and B cell functions. In atopic dermatitis, CD23 regulation is altered, contributing to disease pathology.
low-affinity IgE receptor activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| FCER2 (CD23) | Atopic dermatitis | Knockout mouse or human cell line; measure IgE binding and cytokine release |
| FCER2 (CD23) | Allergic inflammation | Overexpression in B cells; assess IgE synthesis |
| FCER2 (CD23) | Transplantation alloresponse | CD23 knockout in mouse transplant models |
| ADAM10 | CD23 shedding in allergy | ADAM10 knockout or point mutation; measure soluble CD23 |
| IGHE | IgE-mediated allergy | Knock-in of human IgE into mouse |
Atopic Dermatitis
Atopic dermatitis is a chronic inflammatory skin disease characterized by impaired skin barrier and immune dysregulation. CD23 (low-affinity IgE receptor) expression and regulation are altered in atopic dermatitis patients, and soluble CD23 levels correlate with disease severity. Targeting CD23 may provide therapeutic benefit.
Allergic Inflammation and Anaphylaxis
Low-affinity IgE receptor activity contributes to allergic inflammation by modulating IgE-mediated responses. Although non-IgE-mediated anaphylaxis is distinct, CD23 can influence mast cell and basophil activation indirectly. Anti-CD23 therapies are being explored for allergic diseases.
Transplantation Alloresponses
Donor MHC-specific IgE can augment T and B cell alloresponses in a CD23-dependent manner, suggesting a role for low-affinity IgE receptor activity in transplant rejection. This highlights the receptor's broader immunological significance.
From low-affinity IgE receptor activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CD23 mediate IgE binding and signaling? | FCER2 knockout cell line (e.g., Ramos B cells) |
| What is the role of ADAM10 cleavage in CD23 function? | ADAM10 point mutation or knockout |
| Can soluble CD23 modulate IgE synthesis? | Knock-in of soluble CD23 variant |
| How does CD23 contribute to atopic dermatitis? | CD23 overexpression in keratinocytes or mouse model |
| Does CD23 affect T cell alloresponses? | CD23 knockout in mouse transplant model |
| Can anti-CD23 antibodies block IgE binding? | CD23 knock-in with epitope tag for imaging |
How to Study the low-affinity IgE receptor activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Flow cytometry | Cell surface CD23 and IgE binding | Quantify receptor levels and affinity |
| Western blot | CD23 protein and cleavage fragments | Assess ADAM10-mediated shedding |
| Immunoprecipitation | Protein-protein interactions | Identify CD23 signaling partners |
| CRISPR knockout | Gene function loss | Study FCER2 or ADAM10 roles |
| CRISPR point mutation | Specific amino acid function | Map IgE binding site |
| RNA-seq | Transcriptome changes | Identify downstream pathways |
| ELISA | Soluble CD23 and IgE levels | Measure soluble CD23 in supernatants |
| Proximity ligation assay | In situ protein interactions | Visualize CD23 oligomerization |
Flow Cytometry and Binding Assays
Flow cytometry using fluorescently labeled IgE can measure low-affinity IgE receptor activity on cell surfaces. Competitive binding assays with anti-CD23 antibodies can assess specificity.
Western Blotting and Immunoprecipitation
Western blotting detects CD23 protein levels and cleavage products, while immunoprecipitation can identify interacting partners.
CRISPR-Cas9 Genome Editing
CRISPR knockout of FCER2 or ADAM10 allows functional studies of low-affinity IgE receptor activity. Point mutations can dissect binding sites.
RNA Sequencing and Transcriptomics
RNA-seq can reveal changes in gene expression upon CD23 activation or knockout, identifying downstream pathways.
How CRISPR Can Be Used to Study GO:0019769 low-affinity IgE receptor activity
Knockout
CRISPR knockout of FCER2 (CD23) eliminates low-affinity IgE receptor activity, allowing researchers to study its role in IgE binding, B cell activation, and allergic responses. Knockout of ADAM10 prevents CD23 cleavage, increasing membrane-bound CD23.
Point Mutation
Point mutations in the C-type lectin domain of CD23 can abolish IgE binding, helping to map the interaction interface and distinguish low-affinity from high-affinity binding.
Knock-in
Knock-in of tagged CD23 (e.g., GFP or HA) enables real-time imaging and tracking of receptor trafficking and cleavage. Knock-in of human CD23 into mouse models can humanize IgE responses.
Overexpression
Overexpression of CD23 in cell lines or transgenic mice can enhance low-affinity IgE receptor activity, modeling allergic sensitization and allowing study of downstream signaling.
How EDITGENE Supports low-affinity IgE receptor activity Research
Researchers studying low-affinity IgE receptor activity-related genes often need to determine whether a candidate gene is causally involved in receptor function, signaling, or disease. EDITGENE provides comprehensive CRISPR-based services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for low-affinity IgE receptor activity research.
Frequently Asked Questions About low-affinity IgE receptor activity
What is low-affinity IgE receptor activity?
It is a molecular function (GO:0019769) where a cell binds IgE with low affinity via the Fc region and transmits a signal to change cell activity.
What genes are involved in low-affinity IgE receptor activity?
The primary gene is FCER2, which encodes CD23. Other genes include ADAM10, IGHE, and transcription factors like STAT6.
What is CD23?
CD23, also known as FcεRII, is the low-affinity IgE receptor, a C-type lectin involved in IgE regulation and immune cell functions.
How is low-affinity IgE receptor activity regulated?
It is regulated by cytokines (IL-4, IL-13), proteolytic cleavage by ADAM10, and soluble CD23 feedback.
What diseases are associated with low-affinity IgE receptor activity?
Atopic dermatitis, allergic inflammation, and transplantation alloresponses are linked to CD23 function.
What is the difference between high-affinity and low-affinity IgE receptors?
High-affinity receptor (FcεRI) binds IgE strongly and is found on mast cells; low-affinity receptor (CD23) binds weakly and is on B cells and other cells.
How can I study low-affinity IgE receptor activity in the lab?
Use flow cytometry, Western blot, CRISPR knockout, and overexpression models to assess CD23 function.
What is the role of ADAM10 in low-affinity IgE receptor activity?
ADAM10 cleaves CD23, releasing soluble CD23 that modulates IgE responses.
Can CRISPR be used to study low-affinity IgE receptor activity?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression are powerful tools to dissect CD23 biology.
What services does EDITGENE offer for low-affinity IgE receptor research?
EDITGENE provides knockout, point mutation, knock-in, overexpression cell models, CRISPR library screening, and bioinformatics.
Conclusion
GO:0019769 low-affinity IgE receptor activity is a key molecular function mediated primarily by CD23, with important roles in IgE regulation, allergic diseases, and immune cell crosstalk. Understanding its mechanism and regulation offers insights into allergy and transplantation immunology. Advanced CRISPR models and bioinformatics services from EDITGENE can accelerate discoveries in this field.
References
- 1. Cianferoni A. 2021. Non-IgE-mediated anaphylaxis.. J Allergy Clin Immunol 147(4):1123-1131 PMID: 33832694
- 2. Rosenwasser LJ et al.. 2005. Anti-CD23.. Clin Rev Allergy Immunol 29(1):61-72 PMID: 16222084
- 3. Acharya M et al.. 2010. CD23/FcεRII: molecular multi-tasking.. Clin Exp Immunol 162(1):12-23 PMID: 20831712
- 4. Richards ML et al.. 1991. Biology and chemistry of low affinity IgE receptor (Fc epsilon RII/CD23).. Crit Rev Immunol 11(2):65-86 PMID: 1834078
- 5. Delespesse G et al.. 1989. Low-affinity receptor for IgE (FcERII, CD23) and its soluble fragments.. Int Arch Allergy Appl Immunol 90 Suppl 1:41-4 PMID: 2533179
- 6. Lemieux GA et al.. 2007. The low affinity IgE receptor (CD23) is cleaved by the metalloproteinase ADAM10.. J Biol Chem 282(20):14836-44 PMID: 17389606
- 7. Weijler AM et al.. 2026. Donor major histocompatibility complex-specific immunoglobulin E augments the T and B cell alloresponse in a CD23-dependent manner.. Am J Transplant 26(3):467-479 PMID: 41317870
- 8. Halpern M et al.. 1993. Regulation of the low affinity IgE Fc receptor (CD23) in atopic dermatitis.. Int Arch Allergy Immunol 100(3):197-200 PMID: 8453305
