Transgene CD23 expression on lymphoid cells modulates IgE and IgG1 responses.
Transmembrane (m) and soluble (s) forms of CD23 perform activities related to various immune functions. Abnormal expression patterns of CD23 on lymphoid cells have been associated with certain pathologic conditions. To explore the effects of CD23 when it is overexpressed, on lymphoid cell development and immune function in vivo, transgenic mice were generated. These mice overexpressed either mCD23 or a 38-kDa molecular form of sCD23. Transgene expression under the control of Thy-1-regulatory sequences and the mouse Ig heavy chain enhancer (E mu) was prominent in thymus, spleen, bone marrow, and lymph nodes. Cells that expressed the transgenes included most thymocytes, peripheral CD4+ and CD8+ T cells, IgM+/highIgD-/low immature B cells, and IgMlowIgDhigh mature B cells. To resolve the expression pattern in the B cell lineage unambiguously, we used mice that carried a transgene and a disrupted endogenous CD23 gene simultaneously. Neither mCD23 nor sCD23 overexpression caused significant alterations in lymphoid cell maturation. In addition, basal serum levels of IgE and IgG1 proved to be normal. In three different experimental immune response paradigms, mCD23 transgenic, but not sCD23 and nontransgenic mice proved to be impaired in increasing serum levels of polyclonal IgE up to expected levels. In addition, mCD23 transgenic mice showed below normal increases of serum IgG1 levels in two of the three immune responses. In the presence of activated T cells and appropriate lymphokines, B cells from mCD23 mice secreted normal amounts of IgE and IgG1 in vitro, which suggests that there was no serious impairment of the T-B cell contact required for Ig production. In addition, there is no evidence for a significant role of mCD23 in IgE clearance. Therefore, we discuss alternative mechanisms by which mCD23+ B and/or T cells influence Ig production.
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Department of Molecular Cell Biology/Central Nervous System, Ciba-Geigy Limited, Basel, Switzerland.
Eibel
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Le Gros
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van der Putten
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D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015870:Gene Expression; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007156:Immunologic Memory; D051379:Mice; D008822:Mice, Transgenic; D009559:Nippostrongylus / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D017455:Receptors, IgE / Q000235:genetics*; D013154:Spleen / Q000166:cytology
D000909:Antibodies, Helminth; D007074:Immunoglobulin G; D012333:RNA, Messenger; D017455:Receptors, IgE; D007073:Immunoglobulin E