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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Naive CD4 T cells constitutively express CD40L and augment autoreactive B cell survival
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Naive CD4 T cells constitutively express CD40L and augment autoreactive B cell survival

机译:幼稚CD4 T细胞组成性表达CD40L并增加自身反应性B细胞存活

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摘要

Chronic engagement of the B cell receptor by soluble autoantigen leads to reduced B cell survival. Using the Ig and hen egg lysozyme double transgenic mouse model, we demonstrate that the survival of soluble autoantigen-engaged B cells is further reduced in mice lacking CD4 T cells or deficient in CD40. Mixed bone marrow chimera experiments reveal that, under homeostatic conditions, the CD40L-CD40 pathway can augment autoreactive B cell survival in a non-cell-autonomous manner. Naive CD4 T cells are shown to constitutively express CD40L mRNA and protein, although cell surface CD40L abundance is low because of engagement with CD40 on other cells. These observations indicate that the CD40L-CD40 pathway can augment the survival of autoantigen-engaged B cells in the absence of T cell activation. We propose that constitutive CD40L expression by naive CD4 T cells influences the composition of the B cell repertoire and may also affect the homeostasis of other cell types such as regulatory T cells in lymphoid organs.
机译:可溶性自身抗原对B细胞受体的长期参与会导致B细胞存活率降低。使用Ig和鸡蛋的溶菌酶双转基因小鼠模型,我们证明了在缺乏CD4 T细胞或CD40缺乏的小鼠中可溶性自身抗原结合B细胞的存活率进一步降低。混合的骨髓嵌合体实验表明,在稳态条件下,CD40L-CD40途径可以非细胞自主方式增加自身反应性B细胞存活。尽管由于与其他细胞上的CD40结合,细胞表面CD40L的丰度较低,但朴素的CD4 T细胞显示出组成型表达CD40L mRNA和蛋白质。这些观察结果表明,在没有T细胞活化的情况下,CD40L-CD40途径可以增加自身抗原结合的B细胞的存活。我们提出,幼稚的CD4 T细胞组成性CD40L表达影响B细胞库的组成,也可能影响其他细胞类型的稳态,例如淋巴器官中的调节性T细胞。

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