Texido G, Eibel H, Le Gros G, van der Putten H
Department of Molecular Cell Biology/Central Nervous System, Ciba-Geigy Limited, Basel, Switzerland.
J Immunol. 1994 Oct 1;153(7):3028-42.
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.
CD23的跨膜（m）形式和可溶性（s）形式具有与多种免疫功能相关的活性。淋巴细胞上CD23的异常表达模式与某些病理状况有关。为了探究CD23过表达时对体内淋巴细胞发育和免疫功能的影响，构建了转基因小鼠。这些小鼠过表达mCD23或一种38 kDa分子形式的sCD23。在Thy-1调控序列和小鼠Ig重链增强子（Eμ）控制下的转基因表达在胸腺、脾脏、骨髓和淋巴结中很显著。表达转基因的细胞包括大多数胸腺细胞、外周CD4⁺和CD8⁺ T细胞、IgM⁺/高IgD⁻/低未成熟B细胞以及IgM低IgD高成熟B细胞。为了明确解析B细胞谱系中的表达模式，我们使用了同时携带转基因和内源性CD23基因敲除的小鼠。mCD23和sCD23的过表达均未引起淋巴细胞成熟的显著改变。此外，IgE和IgG1的基础血清水平证明是正常的。在三种不同的实验性免疫应答范式中，mCD23转基因小鼠，但不是sCD23转基因小鼠和非转基因小鼠，在将多克隆IgE血清水平升高至预期水平方面被证明存在缺陷。此外，mCD23转基因小鼠在三种免疫应答中的两种中显示出血清IgG1水平低于正常升高。在活化T细胞和适当淋巴因子存在的情况下，来自mCD23小鼠的B细胞在体外分泌正常量的IgE和IgG1，这表明Ig产生所需的T - B细胞接触没有严重受损。此外，没有证据表明mCD23在IgE清除中起重要作用。因此，我们讨论了mCD23⁺ B和/或T细胞影响Ig产生的替代机制。
