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MHC-染色体剂量效应:新生非整倍体鸡中Ia糖蛋白表达增加及B细胞亚群改变的证据。

MHC-chromosome dosage effects: evidence for increased expression of Ia glycoprotein and alteration of B cell subpopulations in neonatal aneuploid chickens.

作者信息

Delany M E, Dietert R R, Bloom S E

机构信息

Department of Poultry and Avian Sciences, Cornell University, Ithaca, NY 14853.

出版信息

Immunogenetics. 1988;27(1):24-30. doi: 10.1007/BF00404440.

DOI:10.1007/BF00404440
PMID:3119472
Abstract

Quantitative variation in the expression of MHC-encoded class II (Ia) glycoproteins has been associated with stages of lymphocyte development and a number of disease conditions. We have used an avian MHC dosage model to study the regulation of Ia expression and the effects of quantitative variation in membrane Ia on B-cell development. Lymphocyte membrane expression of Ia glycoprotein molecules and the frequency of small-versus-large lymphocytes were examined in trisomic line chickens containing either two (disomic), three (trisomic), or four (tetrasomic) copies of the microchromosome encoding the MHC. This was accomplished by quantitative laser flow cytometry analysis of bursa-resident B lymphocytes from neonatal trisomic line chickens. The aneuploids (trisomics and tetrasomics) expressed more cell surface Ia than did normal disomic birds. Furthermore, the aneuploids exhibited a greater frequency of small B lymphocytes as compared to disomic chickens. Dual parameter analysis of Ia quantity and cell size was undertaken to study B lymphocyte subpopulations in these birds. It was observed that the aneuploids had altered frequencies of two distinct subpopulations of cells: (1) an increased percentage of small cells which express high levels of Ia antigen and (2) a decreased percentage of large cells which express medium levels of Ia antigen. These findings support the view that MHC class II genes are regulated and expressed in a dosage-dependent manner. Therefore, increases in the number of MHC copies per cell result in the increased expression of Ia glycoprotein on bursa-resident B cells. The stepwise increase in membrane Ia on trisomic and tetrasomic B cells is correlated, and perhaps casually linked, with progressive degrees of alteration of developing B cell subpopulations in the bursa of aneuploid chicks. These events may ultimately alter the humoral immunity of the aneuploid animals.

摘要

主要组织相容性复合体(MHC)编码的Ⅱ类(Ia)糖蛋白表达的定量变化与淋巴细胞发育阶段及多种疾病状态相关。我们利用禽类MHC剂量模型来研究Ia表达的调控以及膜Ia定量变化对B细胞发育的影响。在含有编码MHC的微染色体两个(二体)、三个(三体)或四个(四体)拷贝的三体品系鸡中,检测了Ia糖蛋白分子的淋巴细胞膜表达以及小淋巴细胞与大淋巴细胞的频率。这是通过对新生三体品系鸡法氏囊中驻留的B淋巴细胞进行定量激光流式细胞术分析来完成的。非整倍体(三体和四体)比正常二体鸡表达更多的细胞表面Ia。此外,与二体鸡相比,非整倍体中小B淋巴细胞的频率更高。对Ia数量和细胞大小进行双参数分析以研究这些鸡中的B淋巴细胞亚群。观察到非整倍体中两个不同细胞亚群的频率发生了改变:(1)表达高水平Ia抗原的小细胞百分比增加,(2)表达中等水平Ia抗原的大细胞百分比降低。这些发现支持了MHCⅡ类基因以剂量依赖性方式被调控和表达的观点。因此,每个细胞中MHC拷贝数的增加导致法氏囊中驻留的B细胞上Ia糖蛋白表达增加。三体和四体B细胞上膜Ia的逐步增加与非整倍体雏鸡法氏囊中发育中的B细胞亚群的逐渐改变程度相关,并且可能存在因果联系。这些事件最终可能改变非整倍体动物的体液免疫。

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Quantitative variation in la antigen expression plays a central role in immune regulation.LA抗原表达的定量变化在免疫调节中起核心作用。
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