Humoral response suppression observed with CD23 transgenics.
CD23, also known as the low affinity IgE receptor (FcepsilonRII), has been hypothesized to have a role in IgE regulation. A new CD23 transgenic mouse was generated using the MHC class I promoter and IgH enhancer to further test the hypothesis that CD23 plays a role in the down-regulation of IgE. Study of three founder lines by FACS showed overexpression to varying extents on both B and T lymphocytes. No alterations in lymphocyte populations was observed. All three founder lines exhibited strong suppression of IgE in response to DNP-keyhole limpet hemocyanin/alum and Nippostrongylus brasiliensis infection compared with that in parental or littermate controls. The founder line exhibiting the highest level of suppression also was less susceptible to Ag-induced systemic anaphylactic shock. Overall, the data support the concept that enhancing CD23 levels can be used to suppress IgE-mediated disease. The mechanism involves decreased IgE synthesis, because the serum half-life of IgE was not altered in transgenics, and enzyme-linked immunospot analysis demonstrated lower IgE-producing cells stimulated by injection of anti-IgD. Transgenics also exhibited significantly decreased IgG1 responses and exhibited lower levels of all Ig isotypes, although this was more variable in different founder lines.
Payet
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ME
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond 23298, USA.
Woodward
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EC
Conrad
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DH
D000534:Alum Compounds / Q000008:administration & dosage; D000707:Anaphylaxis / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage; D000909:Antibodies, Helminth / Q000096:biosynthesis / Q000097:blood; D006207:Half-Life; D006241:Haptens / Q000008:administration & dosage; D006433:Hemocyanins / Q000008:administration & dosage; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000097:blood; D007136:Immunoglobulins / Q000096:biosynthesis*; D016130:Immunophenotyping; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000276:immunology*; D009559:Nippostrongylus / Q000276:immunology; D017455:Receptors, IgE / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D017206:Strongylida Infections / Q000276:immunology
C042158:2,4-dinitrophenyl keyhole limpet hemocyanin; D000534:Alum Compounds; D000888:Antibodies, Anti-Idiotypic; D000909:Antibodies, Helminth; D006241:Haptens; D007136:Immunoglobulins; D017455:Receptors, IgE; C039951:anti-IgD; C041524:aluminum sulfate; D007073:Immunoglobulin E; D006433:Hemocyanins