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首页> 外文期刊>The journal of immunology >Differential Expression of the Adaptor Protein HSH2 Controls the Quantitative and Qualitative Nature of the Humoral Response
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Differential Expression of the Adaptor Protein HSH2 Controls the Quantitative and Qualitative Nature of the Humoral Response

机译:衔接蛋白HSH2的差异表达控制体液反应的定量和定性性质

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Endogenous expression of the adaptor protein hematopoietic Src homology 2-containing adaptor protein (HSH2) is regulated in a dynamic manner during B cell maturation and differentiation. Developing B cells lack detectable HSH2, whereas transitional 1 and 2 B cells in the periphery exhibit increasing levels of expression. Mature follicular B cells exhibit decreased expression of HSH2 compared with transitional 2 B cells, and expression is further downregulated in germinal center B cells. In contrast, marginal zone B cells and B1a/b B cells exhibit high-level HSH2 expression. Regulation of HSH2 expression plays a critical role in determining the outcome of the humoral immune response as demonstrated using HSH2 transgenic (Tg) mice. Constitutive expression of HSH2 in the B lineage at levels comparable to B1a/b B cells results in decreased serum Ig titers for all subclasses with the exception of IgA. HSH2 Tg mice immunized with T-dependent or T-independent Ags exhibit a moderate decrease in the production of Ag-specific IgM, whereas class-switched isotypes are decreased by ~80–90% compared with control mice. Analysis of HSH2 Tg B cell activation in vitro demonstrated that HSH2 selectively regulates the B cell response to TNF family receptors (i.e., CD40 and BAFF-R), but not BCR- or TLR-dependent signals. These data demonstrate that changes in HSH2 expression have profound effects on the humoral immune response.
机译:在B细胞成熟和分化过程中,以动态方式调节衔接子蛋白造血Src同源性2的衔接子蛋白(HSH2)的内源表达。发育中的B细胞缺乏可检测到的HSH2,而外周的过渡1和2 B细胞表现出增加的表达水平。与过渡型2 B细胞相比,成熟的卵泡B细胞表现出HSH2的表达降低,并且生发中心B细胞中的表达进一步下调。相反,边缘区B细胞和B1a / b B细胞表现出高水平的HSH2表达。如使用HSH2转基因(Tg)小鼠所证实的,HSH2表达的调节在确定体液免疫反应的结果中起着至关重要的作用。 B谱系中HSH2的组成型表达水平与B1a / b B细胞相当,导致除IgA以外的所有亚类的血清Ig滴度降低。用T依赖型或T依赖型Ags免疫的HSH2 Tg小鼠的Ag特异性IgM产生适度降低,而与对照小鼠相比,类转换同种型降低了约80-90%。体外对HSH2 Tg B细胞活化的分析表明,HSH2选择性调节B细胞对TNF家族受体(即CD40和BAFF-R)的应答,但不调节BCR或TLR依赖性信号。这些数据表明HSH2表达的变化对体液免疫反应具有深远的影响。

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