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Gene Review

FCER2  -  Fc fragment of IgE, low affinity II,...

Homo sapiens

Synonyms: BLAST-2, C-type lectin domain family 4 member J, CD23, CD23A, CLEC4J, ...
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Disease relevance of FCER2

  • High concentrations of soluble CD23 and L-selectin are found in the serum of patients with B-chronic lymphocytic leukemia (B-CLL) [1].
  • This inhibition was restricted to the MHM6 epitope of CD23 and antibodies to other epitopes [Epstein-Barr virus (EBV) CS-1, EBV CS-2, EBV CS-5 and mAb 25] or occupation of the Fc-binding site by IgE had no or a slightly enhancing effect on aggregation [2].
  • In this study it was investigated whether the control of IL-4 and CD23 levels result in a decrease of the severity of allergic reactions [3].
  • By contrast, the activation antigen CD23 was associated with a higher WBC, higher Rai stage, younger age group, and the presence of lymphadenopathy [4].
  • Similar to its effect on peripheral B cells, Jurkat D1.1 activates B cells from lymphoid organs, as well as a B cell lymphoma clone, RAMOS 266,4CN 3F10 (RAMOS 266), to up-regulate surface CD23 [5].

Psychiatry related information on FCER2

  • Multiple proteins are proteolytically shed from the membrane, including the amyloid precursor protein (APP) involved in Alzheimer's disease, the blood pressure regulating angiotensin converting enzyme (ACE), the low affinity IgE receptor CD23, and the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) [6].

High impact information on FCER2

  • IgE enhances antibody responses via the low-affinity receptor for IgE (FcepsilonRII/CD23) [7].
  • CR2 also can be ligated by CD23, a lectin-like membrane protein that resides on cells that may present antigen to B cells [8].
  • In both rodent and human lymphocytes, Fc epsilon RII on B cells are degraded, and their fragments are released from the cells [9].
  • The R576 allele was associated with higher levels of expression of CD23 by interleukin-4 than the wild-type allele [10].
  • Using this assay, we demonstrate that EBV persists, in the peripheral blood of all seropositive individuals tested, in CD19+, CD23-, and CD80 (B7)- B cells [11].

Chemical compound and disease context of FCER2

  • Role of IgE immune complexes in the regulation of HIV-1 replication and increased cell death of infected U1 monocytes: involvement of CD23/Fc epsilon RII-mediated nitric oxide and cyclic AMP pathways [12].
  • Only 6% of these CD19+/CD5+ patients were CD23-. Overall, CD23- patients had the worse prognostic features compared with CD23+ cases, including anemia (P = 0.03), massive splenomegaly (P = 0.000), high lactate dehydrogenase (P = 0.007), high beta2-microglobulin (P = 0.006), older age (P = 0.001), and male gender (P = 0.02) [13].
  • We have previously reported that ligation of the CD23 molecule with anti-CD23 mAb, or IgE-anti-IgE complexes, leads to phosphoinositide hydrolysis and calcium mobilization through the generation of Inositol (1,4,5) trisphosphate via a process involving a Pertussis toxin insensitive GTP-binding protein [14].
  • In EBV-infected Burkitt lymphoma cells, we have confirmed that high levels of expression are determined largely at the level of gene transcription by performing nuclear run-on transcription analyses and stability determinations of CD23 mRNA in actinomycin D chase experiments [15].
  • The progression of uremia was associated with a gradual increase in soluble CD25, CD23, and especially neopterin levels [16].

Biological context of FCER2


Anatomical context of FCER2


Associations of FCER2 with chemical compounds


Physical interactions of FCER2

  • The mAbs that inhibit the most CD23 binding to CD21 map in SCRs 5 to 8 [25].
  • Exposure of B-CLL cells to PI led to induction of apoptosis, a time- and dose-dependent downregulation of CD23 expression and a decline in DNA binding of transcriptionally active Notch2 [26].
  • However, reconstitution of these X-SCID B cells with gammac enhanced IL-4-mediated responses including STAT6 phosphorylation and DNA binding activity and resulted in increased CD23 expression [27].

Regulatory relationships of FCER2


Other interactions of FCER2

  • The interaction was specifically inhibited by anti-CD11b or anti-CD11c, respectively, and by anti-CD23 MAbs [19].
  • We conclude that ADAM8 could contribute to ectodomain shedding of CD23 and may thus be a potential target for therapeutic intervention in allergy and inflammation [22].
  • We demonstrate that normal human lung endothelial cells (HLECs) are able to express the low affinity receptor for IgE (Fc in RII/CD23), following cell incubation with interleukin 4 or PRBCs [23].
  • Although weaker than in monocytes, CD23 ligation evoked a small secretion of the pro-inflammatory mediators IL-6 and thromboxane B2 [29].
  • We investigated the expression of the low affinity Fc IgE receptor (Fc epsilon RII/CD23) on the human monocytic cell lines U937, THP-1, Mono-Mac-6, and cultured human peripheral blood monocytes under stimulation with human tumour necrosis factor-alpha (TNF-alpha) and other cytokines [30].

Analytical, diagnostic and therapeutic context of FCER2

  • Affinity-purified sCD21 was capable of binding to purified human iC3b and to human recombinant CD23, as assessed by enzyme-linked immunosorbent assay and by using the BIAcore technology [31].
  • Fc epsilon R2/CD23 induction was detectable both by flow cytometry using anti-CD23 mAbs as well as soluble IgE, and by the immunoprecipitation with CD23-specific mAb or IgE of a 45-kD band from 125I-lactoperoxidase-labeled Mo [32].
  • The co-expression of major histocompatibility complex class II molecules and CD23 on CD4+ T lymphocytes in allergic patients, as assessed by the three-color immunofluorescence analysis, indicates that these cells were activated [33].
  • Northern blot analysis showed an increase in CD23 mRNA when activated T cells were cultured in the presence of IL-7 [34].
  • CONCLUSIONS: These data indicate that CD23 negativity is rare in typical B-cell CLL, and CD23 negativity in patients with CD19+/CD5+ is suggestive of mantle cell leukemia a more aggressive disease with poor response to conventional therapy in which newer chemotherapy regimens such as hyper-CVAD may be more effective [13].


  1. Adenosine triphosphate-induced shedding of CD23 and L-selectin (CD62L) from lymphocytes is mediated by the same receptor but different metalloproteases. Gu, B., Bendall, L.J., Wiley, J.S. Blood (1998) [Pubmed]
  2. CD23 and CD21 function as adhesion molecules in homotypic aggregation of human B lymphocytes. Björck, P., Elenström-Magnusson, C., Rosén, A., Severinson, E., Paulie, S. Eur. J. Immunol. (1993) [Pubmed]
  3. Effects of azelastine on the level of serum interleukin-4 and soluble CD23 antigen in the treatment of nasal allergy. Ito, H., Nakamura, Y., Takagi, S., Sakai, K. Arzneimittel-Forschung. (1998) [Pubmed]
  4. Phenotypic markers and BCL-1 gene rearrangements in B-cell chronic lymphocytic leukemia: a Cancer and Leukemia Group B study. Newman, R.A., Peterson, B., Davey, F.R., Brabyn, C., Collins, H., Brunetto, V.L., Duggan, D.B., Weiss, R.B., Royston, I., Millard, F.E. Blood (1993) [Pubmed]
  5. Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help. Lederman, S., Yellin, M.J., Inghirami, G., Lee, J.J., Knowles, D.M., Chess, L. J. Immunol. (1992) [Pubmed]
  6. Structure-activity relationship of hydroxamate-based inhibitors on the secretases that cleave the amyloid precursor protein, angiotensin converting enzyme, CD23, and pro-tumor necrosis factor-alpha. Parkin, E.T., Trew, A., Christie, G., Faller, A., Mayer, R., Turner, A.J., Hooper, N.M. Biochemistry (2002) [Pubmed]
  7. Regulation of antibody responses via antibodies, complement, and Fc receptors. Heyman, B. Annu. Rev. Immunol. (2000) [Pubmed]
  8. The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Fearon, D.T., Carter, R.H. Annu. Rev. Immunol. (1995) [Pubmed]
  9. IgE-binding factors and regulation of the IgE antibody response. Ishizaka, K. Annu. Rev. Immunol. (1988) [Pubmed]
  10. The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. Hershey, G.K., Friedrich, M.F., Esswein, L.A., Thomas, M.L., Chatila, T.A. N. Engl. J. Med. (1997) [Pubmed]
  11. A novel form of Epstein-Barr virus latency in normal B cells in vivo. Miyashita, E.M., Yang, B., Lam, K.M., Crawford, D.H., Thorley-Lawson, D.A. Cell (1995) [Pubmed]
  12. Role of IgE immune complexes in the regulation of HIV-1 replication and increased cell death of infected U1 monocytes: involvement of CD23/Fc epsilon RII-mediated nitric oxide and cyclic AMP pathways. Ouaaz, F., Ruscetti, F.W., Dugas, B., Mikovits, J., Agut, H., Debré, P., Mossalayi, M.D. Mol. Med. (1996) [Pubmed]
  13. The clinical and diagnostic relevance of CD23 expression in the chronic lymphoproliferative disease. DiRaimondo, F., Albitar, M., Huh, Y., O'Brien, S., Montillo, M., Tedeschi, A., Kantarjian, H., Lerner, S., Giustolisi, R., Keating, M. Cancer (2002) [Pubmed]
  14. Ligation of CD23 triggers cyclic AMP generation in human B lymphocytes. Kolb, J.P., Abadie, A., Paul-Eugene, N., Capron, M., Sarfati, M., Dugas, B., Delespesse, G. J. Immunol. (1993) [Pubmed]
  15. Chromatin structure of the lymphocyte Fc epsilon receptor gene (CD23): identification of an upstream transcriptional enhancer. Schubach, W.H., Horvath, G., LeVea, C., Tierney, J. J. Immunol. (1997) [Pubmed]
  16. Balance between IL-1 beta, TNF-alpha, and their specific inhibitors in chronic renal failure and maintenance dialysis. Relationships with activation markers of T cells, B cells, and monocytes. Descamps-Latscha, B., Herbelin, A., Nguyen, A.T., Roux-Lombard, P., Zingraff, J., Moynot, A., Verger, C., Dahmane, D., de Groote, D., Jungers, P. J. Immunol. (1995) [Pubmed]
  17. Genetic markers on chromosome 19p and prenatal diagnosis of HLA class II-deficient combined immunodeficiency. Förster, H.H., Wäsch, R., Kretschmar, T., Mischke, D., Uchańska-Ziegler, B., Ziegler, A., Schmitt, M., Wahn, H.U. Pediatr. Res. (1995) [Pubmed]
  18. Two species of human Fc epsilon receptor II (Fc epsilon RII/CD23): tissue-specific and IL-4-specific regulation of gene expression. Yokota, A., Kikutani, H., Tanaka, T., Sato, R., Barsumian, E.L., Suemura, M., Kishimoto, T. Cell (1988) [Pubmed]
  19. CD23 regulates monocyte activation through a novel interaction with the adhesion molecules CD11b-CD18 and CD11c-CD18. Lecoanet-Henchoz, S., Gauchat, J.F., Aubry, J.P., Graber, P., Life, P., Paul-Eugene, N., Ferrua, B., Corbi, A.L., Dugas, B., Plater-Zyberk, C. Immunity (1995) [Pubmed]
  20. Modulation of IgA, IgE, and IgG Fc receptor expression on human mononuclear phagocytes by 1 alpha,25-dihydroxyvitamin D3 and cytokines. Boltz-Nitulescu, G., Willheim, M., Spittler, A., Leutmezer, F., Tempfer, C., Winkler, S. J. Leukoc. Biol. (1995) [Pubmed]
  21. Haplotype-based association analysis of 56 functional candidate genes in the IBD6 locus on chromosome 19. Tello-Ruiz, M.K., Curley, C., DelMonte, T., Giallourakis, C., Kirby, A., Miller, K., Wild, G., Cohen, A., Langelier, D., Latiano, A., Wedemeyer, N., Lander, E., Schreiber, S., Annese, V., Daly, M.J., Rioux, J.D. Eur. J. Hum. Genet. (2006) [Pubmed]
  22. Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23. Fourie, A.M., Coles, F., Moreno, V., Karlsson, L. J. Biol. Chem. (2003) [Pubmed]
  23. Induction of the CD23/nitric oxide pathway in endothelial cells downregulates ICAM-1 expression and decreases cytoadherence of Plasmodium falciparum-infected erythrocytes. Pino, P., Vouldoukis, I., Dugas, N., Conti, M., Nitcheu, J., Traore, B., Danis, M., Dugas, B., Mazier, D. Cell. Microbiol. (2004) [Pubmed]
  24. Mediation of apoptosis by and antitumor activity of lumiliximab in chronic lymphocytic leukemia cells and CD23+ lymphoma cell lines. Pathan, N.I., Chu, P., Hariharan, K., Cheney, C., Molina, A., Byrd, J. Blood (2008) [Pubmed]
  25. CD23 interacts with a new functional extracytoplasmic domain involving N-linked oligosaccharides on CD21. Aubry, J.P., Pochon, S., Gauchat, J.F., Nueda-Marin, A., Holers, V.M., Graber, P., Siegfried, C., Bonnefoy, J.Y. J. Immunol. (1994) [Pubmed]
  26. Induction of apoptosis by proteasome inhibitors in B-CLL cells is associated with downregulation of CD23 and inactivation of Notch2. Duechler, M., Shehata, M., Schwarzmeier, J.D., Hoelbl, A., Hilgarth, M., Hubmann, R. Leukemia (2005) [Pubmed]
  27. Interleukin-4 signaling in B lymphocytes from patients with X-linked severe combined immunodeficiency. Taylor, N., Candotti, F., Smith, S., Oakes, S.A., Jahn, T., Isakov, J., Puck, J.M., O'Shea, J.J., Weinberg, K., Johnston, J.A. J. Biol. Chem. (1997) [Pubmed]
  28. Stimulation of B lymphocytes via CD72 (human Lyb-2). Kamal, M., Katira, A., Gordon, J. Eur. J. Immunol. (1991) [Pubmed]
  29. Biochemical and functional alterations induced by CD23 ligation in the human promonocytic cell line U937. Paul-Eugene, N., Amirand, C., Ouaaz, F., Ballini, J.P., Mossalayi, D.M., Dugas, B., Kolb, J.P. Immunology (1993) [Pubmed]
  30. Tumour necrosis factor-alpha augments the expression of Fc IgE receptor (Fc epsilon RII/CD23) on human monocytic cell lines and down-regulates interleukin-4-driven Fc epsilon RII expression on monocytes. Gessl, A., Willheim, M., Agis, H., Spittler, A., Schedle, A., Krugluger, W., Förster, O., Boltz-Nitulescu, G. Immunology (1993) [Pubmed]
  31. Human lymphocytes shed a soluble form of CD21 (the C3dg/Epstein-Barr virus receptor, CR2) that binds iC3b and CD23. Frémeaux-Bacchi, V., Bernard, I., Maillet, F., Mani, J.C., Fontaine, M., Bonnefoy, J.Y., Kazatchkine, M.D., Fischer, E. Eur. J. Immunol. (1996) [Pubmed]
  32. Human recombinant interleukin 4 induces Fc epsilon R2/CD23 on normal human monocytes. Vercelli, D., Jabara, H.H., Lee, B.W., Woodland, N., Geha, R.S., Leung, D.Y. J. Exp. Med. (1988) [Pubmed]
  33. Allergen-induced CD23 on CD4+ T lymphocytes and CD21 on B lymphocytes in patients with allergic asthma: evidence and regulation. Gagro, A., Rabatić, S. Eur. J. Immunol. (1994) [Pubmed]
  34. CD23 expression in activated human T cells is enhanced by interleukin-7. Carini, C., Fratazzi, C. Int. Arch. Allergy Immunol. (1996) [Pubmed]
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