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ABSTRACT The single human CD23 gene encodes two protein products differing by six or seven amino acids in the extreme N-terminal cytoplasmic domain. The patterns of expression of CD23a and

CD23b transcripts differs as a function of cell type and cell stimulation, with expression of CD23a being largely restricted to B cells and CD23b synthesis being inducible in a variety of

haematopoietic cells by a range of exogenous stimuli. In this study, short defined sequences of the CD23a and CD23b proximal promoter regions were used to drive expression of exogenous

reporter genes in transiently-transfected B cells exposed to a range of cellular stimuli. The CD23a promoter was activated only by IL-4, whereas the CD23b promoter was stimulated not only by

IL-4, but also by stimulation with anti-μ, and anti-CD40. Deletion mutant analysis illustrated that of the two putative STAT6 binding sites present in the CD23a proximal promoter, deletion

of the first site abrogated IL-4-driven transcriptional activation. Conversely, deletion of both STAT6 binding sites in the CD23b promoter was required before IL-4 sensitivity was lost. When

the same CD23b promoter mutants were studied in the context of anti-CD40 and anti-μ stimulation of transfected cells, deletion of the NF-κB site abrogated anti-CD40-driven transcriptional

activation, but not anti-μ-mediated effects which required additional deletion of putative AP1 sites lying close to the CD23b initiator methionine codon. The data of this report are

consistent with the interpretation that the upstream regions of the CD23a and CD23b isoform coding sequences show distinct sensitivities to agents which induce CD23 protein expression at the

plasma membrane, and that transcriptional activation by discrete stimuli reflects activation of particular transcriptional regulatory factors. Access through your institution Buy or

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January 2023 REFERENCES * Bonnefoy J-Y, Lecoanet-Henchoz S, Gauchat JF _et al_. Structure and functions of CD23 _Int Rev Immunol_ 1997 16: 113–128 Article  CAS  PubMed  Google Scholar  *

Delespesse G, Suter U, Mossalayi D _et al_. Expression, structure and function of the CD23 antigen _Adv Immunol_ 1991 49: 149–191 Article  CAS  PubMed  Google Scholar  * Delespesse G,

Sarfati M, Wu CY, Fournier S, Letellier M . The low affinity receptor for IgE _Immunol Rev_ 1992 125: 77–97 Article  CAS  PubMed  Google Scholar  * Suter U, Bastos R, Hofstetter H .

Molecular structure of the gene and the 5′ flanking regions of the human lymphocyte immunoglobulin E receptor _Nucleic Acid Res_ 1987 15: 7295–7308 Article  CAS  PubMed  PubMed Central 

Google Scholar  * Soilleux EJ, Barten R, Trowsdale J . DC-SIGN; a related gene, DC-SIGNR; and CD23 form a cluster on 19p13 _J Immunol_ 2000 165: 2937–2942 Article  CAS  PubMed  Google

Scholar  * Yokota A, Kikutani H, Tanaka T _et al_. Two species of human Fc epsilon receptor II (FcεRII/CD23): tissue-specific and IL-4 specific regulation of gene expression _Cell_ 1988 55:

611–618 Article  CAS  PubMed  Google Scholar  * Yokota A, Yukawa K, Yamamoto A _et al_. Two forms of the low affinity receptor for IgE differentially mediate endocytosis and phagocytosis;

identification of the critical cytoplasmic domains _Proc Natl Acad Sci USA_ 1992 89: 5030–5034 Article  CAS  PubMed  PubMed Central  Google Scholar  * Soussi GA, Lamkhioued B, Masao M _et

al_. Molecular charaterisation of the low-affinity IgE receptor FceRII/CD23 expressed by human eosinophils _Int Immunol_ 1998 10: 395–404 Article  Google Scholar  * Schubach WH, Horvath G,

LeVea C, Tierney J . Chromatin structure of the lymphocyte Fc epsilon receptor gene (CD23): identification of an upstream transcriptional enhancer _J Immunol_ 1997 158: 2228–2235 CAS  PubMed

  Google Scholar  * Shieh B, Schultz J, Guinness M, Lacy J . Regulation of human IgE receptor (FcεRII/CD23) by Epstein-Barr virus (EBV: Ku autoantigen binds specifically to an EBV-responsive

enhancer of CD23 _Int Immunol_ 1997 9: 1885–1895 Article  CAS  PubMed  Google Scholar  * Seidel HM, Milocco LH, Lamb P, Darnell JE, Stein RB, Rosen J . Spacing of palindromic half sites as

a determinant of selective STAT (signal transducers and activator of transcription) DNA binding and transcriptional activity _Proc Natl Acad Sci USA_ 1995 92: 3041–3045 Article  CAS  PubMed

  PubMed Central  Google Scholar  * Köhler I, Rieber EP . Allergy-associated Iε and Fcε receptor II (CD23b) activated via binding of an interleukin-4-induced factor of a novel response

element _Eur J Immunol_ 1993 23: 3066–3071 Article  PubMed  Google Scholar  * Park H-J, So E-Y, Lee C-E . Interferon-γ-induced factor binding to the interleukin-4-responsive element of the

CD23b promoter in human tonsillar mononuclear cells: role int ransient up-regulation of the interleukin-4-induced CD23b mRNA _Mol Immunol_ 1998 35: 239–247 Article  CAS  PubMed  Google

Scholar  * Baeuerle P . The inducible transcriptional activator NF-: regulation by distinct protein subunits _Biochem Biophy Acta_ 1991 1072: 63–80 CAS  Google Scholar  * Czerny T, Schaffner

G, Busslinger M . DNA sequence recognition by Pax proteins: bipartite structure of the paired domain and its binding site _Genes Dev_ 1993 7: 2048–2061 Article  CAS  PubMed  Google Scholar

  * Hawker KL, Vass JK, Ozanne BW . Isolation of novel, transcriptionally active AP-1 binding sites: implications for cellular transformation _Oncogene_ 1996 13: 283–292 CAS  PubMed  Google

Scholar  * Pollock R, Treisman R . A sensitive method for the determination of protein binding specificity _Nucleic Acid Res_ 1990 18: 6197–6204 Article  CAS  PubMed  PubMed Central  Google

Scholar  * Adams B, Dorfler P, Aguzzi A _et al_. _Pax_-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS and adult testis _Genes Dev_ 1992 6:

1589–1607 Article  CAS  PubMed  Google Scholar  * Kozmik Z, Wang S, Dorfler P, Adams B, Busslinger M . The promoter of the CD19 gene is a target for the B cell-specific transcription factor

BSAP _Mol Cell Biol_ 1992 12: 2662–2672 Article  CAS  PubMed  PubMed Central  Google Scholar  * Urbanek P, Wang Z-Q, Fetka I, Wagner EF, Busslinger M . Complete block of early B cell

differentiation and altered patterning of the posterior midbrain in mice lacking _Pax_-5/ BSAP _Cell_ 1994 79: 901–912 Article  CAS  PubMed  Google Scholar  * Wakatsuki Y, Neurath MF, Max

EE, Strober W . The B cell specific transcription factor BSAP regulates B cell proliferation _J Exp Med_ 1994 179: 1099–1108 Article  CAS  PubMed  Google Scholar  * Capello D, Gaidano G .

Molecular pathophysiology of indolent lymphoma _Haematologica_ 2000 85: 195–201 CAS  PubMed  Google Scholar  * Swendeman S, Thorely-Lawson DA . The activation antigen Blast 2, when shed, is

an autocrine growth factor for normal and transformed B cells _EMBO J_ 1987 6: 1637–1642 Article  CAS  PubMed  PubMed Central  Google Scholar  * Gordon J, Flores-Romo L, Cairns JA _et al_.

CD23: a multi-functional receptor/lymphokine? _Immunol Today_ 1989 10: 153–156 Article  CAS  PubMed  Google Scholar  * Valle A, Zuber CE, Defrance T, Djossou O, De Rie M, Banchereau J .

Activation of human B lymphocytes through CD40 and interleukin 4 _Eur J Immunol_ 1989 19: 1463–1467 Article  CAS  PubMed  Google Scholar  * Cairns JA, Flores-Romo L, Millsum MJ _et al_.

Soluble CD23 is released by B lymphocytes cycling in response to interleukin-4 and anti-Bp50 (CDw40) _Eur J Immunol_ 1988 18: 349 Article  CAS  PubMed  Google Scholar  * Burlinson EL,

Pringle HM, Ozanne BW, Cushley W . Anti-immunoglobulin and anti-CD40 stimulation induces CD25 expression by resting human tonsillar B lymphocytes _Immunol Lett_ 1995 45: 93–98 Article  CAS 

PubMed  Google Scholar  * Burlinson EL, Graber P, Bonnefoy J-Y, Ozanne BW, Cushley W . Soluble CD40 ligand induces expression of CD25 and CD23 in resting human B lymphocytes _Eur J Immunol_

1996 26: 1069–1073 Article  CAS  PubMed  Google Scholar  * Challa A, Pound JD, Armitage RJ, Gordon J . Epitope-dependent synergism and antagonism between CD40 antibodies and soluble CD40

ligand for the regaltion of CD23 expression and IgE synthesis in human B cells _Allergy_ 1999 54: 576–583 Article  CAS  PubMed  Google Scholar  * Hanissian SH, Geha RS . Jak3 is associated

with CD40 and is critical for CD40 induction of gene expression in B cells _Immunity_ 1997 6: 379–387 Article  CAS  PubMed  Google Scholar  * Berberich I, Shu GL, Clark EA . Cross-linking

CD40 on B cells rapidly activates nuclear factor-kappa B _J Immunol_ 1994 153: 4357–4366 CAS  PubMed  Google Scholar  * Hewitt EL, Ozanne BW, Cushley W . Negative Regulation of the IL-2Rα

chain (CD25) in human B lymphocytes _Cytokine_ 1997 8: 982–991 Article  Google Scholar  * McKay CE, Hewitt EL, Ozanne BW, Cushley W . A functional role for interleukin-(IL)-4-driven cyclic

AMP accumulation in human B lymphocytes _Cytokine_ 2000 12: 731–736 Article  CAS  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of

Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK M-A Ewart & W Cushley * CRC Beatson Institute for

Cancer Research, Switchback Road, Glasgow, G61 1BD, Scotland, UK B W Ozanne Authors * M-A Ewart View author publications You can also search for this author inPubMed Google Scholar * B W

Ozanne View author publications You can also search for this author inPubMed Google Scholar * W Cushley View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHOR Correspondence to W Cushley. ADDITIONAL INFORMATION This study was supported in part by a grant from the Biotechnology & Biological Sciences Research Council

initiative in Integration of Cellular Responses. MAE was supported by a Medical Research Council post-graduate studentship. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE

CITE THIS ARTICLE Ewart, MA., Ozanne, B. & Cushley, W. The CD23a and CD23b proximal promoters display different sensitivities to exogenous stimuli in B lymphocytes. _Genes Immun_ 3,

158–164 (2002). https://doi.org/10.1038/sj.gene.6363848 Download citation * Received: 14 November 2001 * Accepted: 02 December 2001 * Published: 21 May 2002 * Issue Date: 01 May 2002 * DOI:

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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * CD23 * transcription * lymphocytes