FCER2 (Fc fragment of IgE, low affinity II, receptor for (CD23))

2011-06-01   Reha Toydemir , Mohamed Salama 

Department of Pathology, University of Utah, ARUP Laboratories, Salt Lake City, Utah, USA





The gene is localized to the short arm of chromosome 19. It contains 11 exons, and spans 13390 bps on minus strand.


Normally expressed in B-cells. Its expression has been shown on T-cells, Langerhans cells, monocytes, macrophages, platelets, and eosinophils as well.
Through alternative splicing 2 major isoforms are produced, FCER2a (CD23a) and FCER2b (CD23b), both of which are expressed on B-cells. FCER2a is constitutively expressed, whereas FCER2b is induced by several cytokines, especially by IL4. There are 3 other splice forms, whose biological significance remains to be determined.





Essential role in the regulation of IgE production as well as differentiation of B cells.


FCER2 is a Ca2+-dependent C-type lectin. The protein in humans contains 321 amino acids and has a molecular weight of 45 kDa. It has a single membrane-spanning domain. The extracellular domain consists of an alpha-helical coiled coil domain, a lectin head, followed by a short tail region containing an inverse RGD sequence. The coiled coil domain and the lectin head section are critical for the formation of trimers, and IgE binding, respectively. The RGD sequence is a common recognition site of integrins. Through an autocatalytic process involving matrix metalloproteases, the membrane-bound FCER2 is turned into a series of soluble fragments (sFCER2) of molecular weight ranging between 17 and 37 kDa. The soluble forms are also biologically active.


FCER2 expression was first described in the thymic medullary B-lymphocytes, and subsequently, in a population of large thymic B-cells with dendritic features which were referred to as asteroid cells. FCER2 is mainly expressed on B cells. It is also expressed on T cells, Langerhans cells, monocytes, macrophages, platelets, and eosinophils. On B cells 2 isoforms are present: a constitutively active form (FCER2a) and an inducible form (FCER2b).
FCER2 expression is upregulated by its own ligand, i.e. IgE. Furthermore, upon treatment with IL4, increased FCER2 expression can be observed in several cell types including eosinophils, neutrophils, macrophages, monocytes, and T cells. In addition, EBV induces CD23 transcription through a regulatory element in intron 1 of FCER2a.
FCER2 expression levels are differentially higher (70%) in mediastinal diffuse large B-cell lymphoma (med-DLBCL) and lower in nonmediastinal nodal DLBCL (15%) and extranodal DLBCL (9%).


Although FCER2 expression is mainly localized to the surface of B-lymphocytes, it is widely distributed on the surface of various other cells including follicular dendritic cells (FDC), and even airway smooth muscle cells.


FCER2 is the low-affinity immunoglobin E receptor. It mediates various biological functions. Mainly, it is involved in the down regulation of IgE production by B cells. However, because of its ability to associate with various ligands, its effects on IgE regulation might be stimulatory as well. In fact, FCER2 has been implicated in a variety of cellular functions ranging from cellular adhesion, antigen presentation, growth and differentiation of B and T cells, rescue from apoptosis, release of cytotoxic mediators, and regulation of IgE synthesis.
FCER2 displays susceptibility to proteolytic cleavage which produces a soluble form of FCER2. As the soluble FCER2 does not have the ability to bind to the cell surface, this results in disruption of the feedback inhibition mechanism and increase of IgE production. As a result, soluble FCER2 has mitogenic properties. Furthermore, the proteolytic cleavage of FCER2 is probably the basis of various allergic reactions.
These observations have been supported by cellular and animal models. Antibodies directed against the soluble FCER2 have been shown to inhibit the synthesis of IgE, while cross linking of membrane-bound FCER2 inhibits B-cell growth and differentiation. Furthermore, FCER2-deficient mice produce higher levels of IgE, whereas mice overexpressing membrane-bound FCER2 exhibit weaker IgE responses.
Lumiliximab is an anti-CD23 antibody that is proposed in the therapy of chronic lymphocytic leukemia (CLL). Lumiliximab binds to cell surface membrane FCER, and induce apoptosis. Although previous reports indicated activation of the caspase cascade, the exact mechanism for apoptosis remains to be elucidated.


At this time a paralogous gene is not known in humans. It does not show similarity to FCER1, the other member of the immunoglobin E receptor family.
Orthologues have been shown in mouse, rat and cow, with up to 58% homology at the protein level. However, some of the domains required for the proper function of human FCER2 is absent in orthologues. For example, the murine FCER2 does not have the RGD motif nor does it retain the IgE-binding affinity.



An arginine to tryptophane substitution of amino acid 62 (p.R62W) have been suggested to affect the receptor function and the mitogenic role of the protein. This suggestion was based on in vitro studies which showed the mutant protein was resistant to proteolytic cleavage following treatment with a broad range of proteases.



Implicated in

Med-DLBCL is a subtype of DLBCL that arise in the mediastinum from putative thymic B-cell origin. Its clinical, immunophenotypic, and genotypic features are distinctive. However, it has significant morphologic and immunophenotypic similarities with classical Hodgkin lymphoma (CHL) involving mediastinum. Since the prognosis and the first line of therapy for these conditions differ significantly, previous studies highlighted the usefulness of CD23 expression in the differential diagnosis of these conditions. Up to 85% of med-DLBCL patients are positive for FCER2, whereas only 10% of CHL patients show a weak FCER2 staining, suggesting that FCER2 might be helpful to distinguish between med-DLBCL and CHL.
Entity name
Chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL)
CD23 positivity is noted in most cases of CLL/SLL and is used to differentiate CLL/SLL from mantle cell lymphoma that shares the CD5+ B-cell phenotype. The lack of CD23 in mantle cell lymphoma along with the dim expression of CD20 and light chain in CLL often help in this important distinction given the difference in prognosis and therapeutic options. However, some case of CLL/SLL may have an atypical phenotype including the lack of CD23 expression; posing diagnostic difficulty.
NMZL is a rare form of non-Hodgkin lymphoma with primary presentation in the lymph node in the absence of clinical evidence of prior or concurrent involvement of extranodal sites or spleen. In a comprehensive study, FCER2 was found to highlight neoplastic cells in a case in which the staining was diffuse but weakly positive. Furthermore, the FCER2 staining highlighted residual and disrupted follicular dendritic cell (FDC) meshwork in 40% of the NMZL cases that were also highlighted by CD21 staining.
Entity name
CD23 positivity by immunohistochemical analysis has been recently linked to a specific anatomic site in FL. Thorns et al. (2007) found that FLs in inguinal lymph nodes were more commonly CD23+ compared with FL from other anatomic sites. Katzenberger et al. (2009) demonstrated a high proportion of CD23+ cases in FLs with a diffuse growth pattern and a specific chromosomal alteration (deletion 1p36). CD23 expression in FL was most recenlty reported to be associated with favorable outcome by Olteano et al. (2011) who also reported that CD23 positivity was more common in inguinal lymph nodes and in low-grade cases. They postulated that CD23 expression is at least partially modulated by the tissue- and/or host-specific factors (such as anatomic site or lower histologic grade) and suggested CD23 expression may be a surrogate for a certain host-specific (possibly, immune) environment that is associated with a more indolent disease course and, thus, with a favorable outcome.


Pubmed IDLast YearTitleAuthors
196042642009Functional and clinical consequences of Fc receptor polymorphic and copy number variants.Bournazos S et al
155690532004CD23 expression in mediastinal large B-cell lymphomas.Calaminici M et al
16830541991Phenotype and topography of human thymic B cells. An immunohistologic study.Fend F et al
24474581987The human thymus contains a novel population of B lymphocytes.Isaacson PG et al
189782082009A distinctive subtype of t(14;18)-negative nodal follicular non-Hodgkin lymphoma characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36.Katzenberger T et al
79897551994Regulation of the human IgE receptor (Fc epsilon RII/CD23) by EBV. Localization of an intron EBV-responsive enhancer and characterization of its cognate GC-box binding factors.Lacy J et al
173018282007Polymorphism R62W results in resistance of CD23 to enzymatic cleavage in cultured cells.Meng JF et al
211731232011CD23 expression in follicular lymphoma: clinicopathologic correlations.Olteanu H et al
180327102008Mediation of apoptosis by and antitumor activity of lumiliximab in chronic lymphocytic leukemia cells and CD23+ lymphoma cell lines.Pathan NI et al
109195012000Murine models of inflammation: role of CD23.Riffo-Vasquez Y et al
198642322009Immunoarchitectural patterns in nodal marginal zone B-cell lymphoma: a study of 51 cases.Salama ME et al
192233732010The value of CD23 expression as an additional marker in distinguishing mediastinal (thymic) large B-cell lymphoma from Hodgkin lymphoma.Salama ME et al
179804182007FCER2: a pharmacogenetic basis for severe exacerbations in children with asthma.Tantisira KG et al
174932352007Significant high expression of CD23 in follicular lymphoma of the inguinal region.Thorns C et al
107923502000The role of CD23 in allergic disease.Tsicopoulos A et al

Other Information

Locus ID:

NCBI: 2208
MIM: 151445
HGNC: 3612
Ensembl: ENSG00000104921


dbSNP: 2208
ClinVar: 2208
TCGA: ENSG00000104921


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Hematopoietic cell lineageKEGGko04640
Hematopoietic cell lineageKEGGhsa04640
Epstein-Barr virus infectionKEGGhsa05169
Epstein-Barr virus infectionKEGGko05169
Immune SystemREACTOMER-HSA-168256
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Signal TransductionREACTOMER-HSA-162582
Signaling by NOTCHREACTOMER-HSA-157118
Signaling by NOTCH2REACTOMER-HSA-1980145
NOTCH2 intracellular domain regulates transcriptionREACTOMER-HSA-2197563
Interleukin-4 and 13 signalingREACTOMER-HSA-6785807
Interleukin-10 signalingREACTOMER-HSA-6783783

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
177034122007Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes.100
236973682013General mechanism for modulating immunoglobulin effector function.74
179804182007FCER2: a pharmacogenetic basis for severe exacerbations in children with asthma.48
127773992003Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23.43
161722562005The structure of human CD23 and its interactions with IgE and CD21.41
208317122010CD23/FcεRII: molecular multi-tasking.37
228026562012Crystal structure of IgE bound to its B-cell receptor CD23 reveals a mechanism of reciprocal allosteric inhibition with high affinity receptor FcεRI.34
186361242008Polymorphisms in the estrogen receptor 1 and vitamin C and matrix metalloproteinase gene families are associated with susceptibility to lymphoma.32
175767662007Soluble CD23 monomers inhibit and oligomers stimulate IGE synthesis in human B cells.28
202374962010New genetic associations detected in a host response study to hepatitis B vaccine.27


Reha Toydemir ; Mohamed Salama

FCER2 (Fc fragment of IgE, low affinity II, receptor for (CD23))

Atlas Genet Cytogenet Oncol Haematol. 2011-06-01

Online version: http://atlasgeneticsoncology.org/gene/44222/fcer2-(fc-fragment-of-ige-low-affinity-ii-receptor-for-(cd23))