Oligomerization of CD23 Regulation of IgE Production Requires

Here we describe the production of a rabbit polyclonal Ab (RAS1) raised against the stalk of murine CD23. RAS1 inhibits release of CD23 from the surface of both M12 and B cells resulting in an increase of CD23 on the cell surface. Despite this increase, these cells are unable to bind IgE as determined by FACS. CD23 has previously been shown to bind IgE with both a high (4–10 (cid:1) 10 7 M (cid:2) 1 ) and low (4–10 (cid:1) 10 6 M (cid:2) 1 ) affinity. Closer examination by direct binding of 125 I-IgE revealed that RAS1 blocks high affinity binding while having no effect on low affinity binding. These data support the model proposing that oligomers of CD23 mediate high affinity IgE binding. These experiments suggest that RAS1 binding to cell surface CD23 results in a shift from oligomers to monomers, which, according to the model, only bind IgE with low affinity. These experiments also suggest that high affinity binding of IgE is required for IgE regulation by CD23 and is demonstrated by the fact that treatment of Ag/Alum-immunized mice treated with RAS1 results in a significant increase in IgE production similar to the levels seen in CD23-deficient mice. These mice also had significantly decreased levels of serum soluble CD23 and Ag-specific IgG1. RAS1 had no effect on IgE or Ag-specific IgG1 production in CD23-deficient mice. The Journal of Immunology, 2001, 167: 3139–3145.

[1]  P. Wingfield.  Production of Recombinant Proteins , 2002 .

[2]  D. Conrad,et al.  Suppression of IgE Responses in CD23-Transgenic Animals Is Due to Expression of CD23 on Nonlymphoid Cells1 , 2001, The Journal of Immunology.

[3]  B. Heyman,et al.  Restoration of the Antibody Response to IgE/Antigen Complexes in CD23-Deficient Mice by CD23+ Spleen or Bone Marrow Cells1 , 2000, The Journal of Immunology.

[4]  P. Brams,et al.  In vitro IgE inhibition in B cells by anti-CD23 monoclonal antibodies is functionally dependent on the immunoglobulin Fc domain. , 2000, International journal of immunopharmacology.

[5]  D. Conrad,et al.  Humoral response suppression observed with CD23 transgenics. , 1999, Journal of immunology.

[6]  D. Conrad,et al.  Production of a Chimeric Form of CD23 That Is Oligomeric and Blocks IgE Binding to the FcεRI , 1998, The Journal of Immunology.

[7]  J. Bonnefoy,et al.  Binding of Anti-CD23 Monoclonal Antibody to the Leucine Zipper Motif of FcεRII/CD23 on B Cell Membrane Promotes Its Proteolytic Cleavage , 1998, The Journal of Biological Chemistry.

[8]  D. Earnshaw,et al.  CD23 (FcepsilonRII) release from cell membranes is mediated by a membrane-bound metalloprotease. , 1998, The Biochemical journal.

[9]  P. Murdock,et al.  IgE secretion is attenuated by an inhibitor of proteolytic processing of CD23 (FcεRII) , 1997 .

[10]  D. Conrad,et al.  B cell activation and Ig, especially IgE, production is inhibited by high CD23 levels in vivo and in vitro. , 1997, Cellular immunology.

[11]  F. Finkelman,et al.  Induction of B cell apoptosis by co-cross-linking CD23 and sIg involves aberrant regulation of c-myc and is inhibited by bcl-2. , 1997, International immunology.

[12]  R. Armitage,et al.  Expression of trimeric CD40 ligand in Pichia pastoris: use of a rapid method to detect high-level expressing transformants. , 1997, Gene.

[13]  R J Armitage,et al.  Structural characteristics of CD40 ligand that determine biological function. , 1994, Seminars in immunology.

[14]  H. Eibel,et al.  Transgene CD23 expression on lymphoid cells modulates IgE and IgG1 responses. , 1994, Journal of immunology.

[15]  H. Kikutani,et al.  The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[16]  G. Köhler,et al.  Negative feedback regulation of IgE synthesis by murine CD23 , 1994, Nature.

[17]  H. Eibel,et al.  Mice deficient in CD23 reveal its modulatory role in IgE production but no role in T and B cell development. , 1994, Journal of immunology.

[18]  H. Bazin,et al.  Inhibition of an in vivo antigen-specific IgE response by antibodies to CD23. , 1993, Science.

[19]  N. Chiorazzi,et al.  Anti-CD23 monoclonal antibodies: comparisons of epitope specificities and modulating capacities for IgE binding and production. , 1993, Hybridoma.

[20]  S. Fournier,et al.  The Low‐Affinity Receptor for IgE , 1992, Immunological reviews.

[21]  D. Conrad,et al.  Characterization of new rat anti-mouse IgE monoclonals and their use along with chimeric IgE to further define the site that interacts with FcϵRII and FcϵRI , 1991 .

[22]  E. Rieber,et al.  IgE‐dependent antigen focusing by human B lymphocytes is mediated by the low‐affinity receptor for IgE , 1990, European journal of immunology.

[23]  H. Kikutani,et al.  Two species of human Fcε receptor II ( FcεRII CD23 ): Tissue-specific and IL-4-specific regulation of gene expression , 1988, Cell.

[24]  J. Banchereau,et al.  A monoclonal anti-IgE antibody against an epitope (amino acids 367-376) in the CH3 domain inhibits IgE binding to the low affinity IgE receptor (CD23). , 1988, Journal of immunology.

[25]  D. Conrad,et al.  Superinduction of low affinity IgE receptors on murine B lymphocytes by lipopolysaccharide and IL-4. , 1988, Journal of immunology.

[26]  D. Conrad,et al.  The murine lymphocyte receptor for IgE. IV. The mechanism of ligand-specific receptor upregulation on B cells. , 1987, Journal of immunology.

[27]  G. Delespesse,et al.  Purification and partial biochemical characterization of IgE-binding factors secreted by a human B lymphoblastoid cell line. , 1987, Immunology.

[28]  D. Conrad,et al.  Characterization of a monoclonal antibody directed against the murine B lymphocyte receptor for IgE. , 1987, Journal of immunology.

[29]  G. Delespesse,et al.  Cloning and expression of the cDNA coding for a human lymphocyte IgE receptor. , 1987, The EMBO journal.

[30]  D. Conrad,et al.  The murine lymphocyte receptor for IgE. III. Use of chemical cross-linking reagents to further characterize the B lymphocyte Fc epsilon receptor. , 1985, Journal of immunology.

[31]  W. Paul,et al.  Frequency of B lymphocytes responsive to anti-immunoglobulin , 1982, The Journal of experimental medicine.

[32]  M. Gefter,et al.  Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus. , 1979, Journal of immunology.

[33]  D H Sachs,et al.  Establishment and characterization of BALB/c lymphoma lines with B cell properties. , 1979, Journal of immunology.

[34]  H. Metzger,et al.  Isolation of IgE from reaginic rat serum. , 1974, Journal of immunology.

[35]  P. Murdock,et al.  IgE secretion is attenuated by an inhibitor of proteolytic processing of CD23 (Fc epsilonRII). , 1997, European journal of immunology.

[36]  D. Conrad.  FcεRII/CD23: The Low Affinity Receptor for IgE , 1990 .

[37]  A. Beavil,et al.  a-Helical coiled-coil stalks in the low-affinity receptor for IgE (FcERII/CD23) and related C-type lectins , 2022 .