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μ转基因小鼠的内源性Ig产生。II. 抗Ig反应性和明显的双同种异型表达。

Endogenous Ig production in mu transgenic mice. II. Anti-Ig reactivity and apparent double allotype expression.

作者信息

Imanishi-Kari T, Huang C A, Iacomini J, Yannoutsos N

机构信息

Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.

出版信息

J Immunol. 1993 Apr 15;150(8 Pt 1):3327-46.

PMID:8468474
Abstract

In 17.2.25 mu transgenic mice (M54, M95), many of the expressed Ig, whether encoded by the transgene or endogenous H chain genes, react with Ig. IgM antibodies encoded by the 17.2.25 mu transgene transfected into J558L myeloma cells are also Ig reactive. In addition, anti-Ig reactivity was manifested by antibodies of the IgM, IgG, and IgA isotypes from the transgenic mice, suggesting that this characteristic reactivity is associated with VH and VL domains of these antibodies. These antibodies bind the (Fab')2 fragment of mouse IgG1 mAb known to be directed against C mu allotypic determinants. This finding could account for the so called "double producer" B cells found in mu transgenic mice and previously identified in serologic assays conducted with two different anti-mu allotypic reagents. In transgenic mice, a high frequency of the antibodies encoded by the transgene or endogenous H chain genes react with polyclonal and monoclonal antiidiotypic antibodies raised against the 17.2.25 Id. The idiotypic and/or antiidiotypic reactivity displayed by antibodies derived from these transgenic mice is similar to that of antibodies expressed by neonatal B cells of normal mice. Thus, our data suggest that transgene expression can play an important role in shaping the endogenous repertoire of antibody specificities.

摘要

在17.2.25μ转基因小鼠(M54、M95)中,许多表达的Ig,无论由转基因还是内源性重链基因编码,都与Ig发生反应。转染到J558L骨髓瘤细胞中的17.2.25μ转基因编码的IgM抗体也具有Ig反应性。此外,转基因小鼠的IgM、IgG和IgA同种型抗体均表现出抗Ig反应性,这表明这种特征性反应性与这些抗体的VH和VL结构域相关。这些抗体结合已知针对Cμ同种异型决定簇的小鼠IgG1单克隆抗体的(Fab')2片段。这一发现可以解释在μ转基因小鼠中发现的所谓“双产生”B细胞,以及先前在使用两种不同的抗μ同种异型试剂进行的血清学检测中鉴定出的B细胞。在转基因小鼠中,由转基因或内源性重链基因编码的抗体中有很高比例与针对17.2.25独特型产生的多克隆和单克隆抗独特型抗体发生反应。这些转基因小鼠产生的抗体所显示的独特型和/或抗独特型反应性与正常小鼠新生B细胞表达的抗体相似。因此,我们的数据表明转基因表达在塑造内源性抗体特异性库方面可以发挥重要作用。

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