Dual immunoglobulin light chain B cells: Trojan horses of autoimmunity?

Dual immunoglobulin light chain B cells: Trojan horses of autoimmunity?
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DOI:
10.1016/j.coi.2014.01.012
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发表时间:
2014-04
影响因子:
7
通讯作者:
Pelanda, Roberta
Pelanda, Roberta
中科院分区:
医学2区
文献类型:
--
作者:
Pelanda, Roberta

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受体编辑是B细胞耐受性的主要机制,也可导致免疫球蛋白轻链基因座处的等位基因包含和共表达两种不同免疫球蛋白轻链并因此产生两种抗体特异性的B细胞的发育。大多数等位基因包含的B细胞表达两条κ链,尽管也观察到罕见的双λ细胞。此外,这些细胞通常共表达自身反应性和非自身反应性抗体。因此,等位基因所包含的B细胞可以像“特洛伊木马”一样运作:非自身反应性抗原受体的表达和功能可能促进它们成熟、活化和终末分化为也表达和分泌自身抗体的效应细胞。事实上,在一些自身免疫小鼠中,双κ B细胞大量扩增为效应B细胞亚群,从而表明它们可能在疾病中发挥重要作用。
Receptor editing, a major mechanism of B cell tolerance, can also lead to allelic inclusion at the immunoglobulin light chain loci and the development of B cells that co-express two different immunoglobulin light chains and, therefore, two antibody specificities. Most allelically included B cells express two κ chains, although rare dual-λ cells are also observed. Moreover, these cells typically co-express an autoreactive and a nonautoreactive antibody. Thus, allelically included B cells could operate like “Trojan horses”: expression and function of the nonautoreactive antigen receptors might promote their maturation, activation, and terminal differentiation into effector cells that also express and secrete autoantibodies. Indeed, dual-κ B cells are greatly expanded into effector B cell subsets in some autoimmune mice, thus indicating they might play an important role in disease.
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