Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, CO 80206, USA.
Curr Opin Immunol. 2014 Apr;27:53-9. doi: 10.1016/j.coi.2014.01.012. Epub 2014 Feb 15.
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 coexpress 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 coexpress 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.
受体编辑是 B 细胞耐受的主要机制,也可导致免疫球蛋白轻链基因座的等位基因包含,并产生同时表达两种不同免疫球蛋白轻链的 B 细胞,因此表达两种抗体特异性。大多数等位基因包含的 B 细胞表达两种 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一种自身反应性和一种非自身反应性抗体。因此,等位基因包含的 B 细胞可能像“特洛伊木马”一样发挥作用:非自身反应性抗原受体的表达和功能可能促进其成熟、激活和终末分化为效应细胞,这些效应细胞也表达和分泌自身抗体。事实上,在某些自身免疫小鼠中,双 κ B 细胞大量扩增为效应 B 细胞亚群,这表明它们可能在疾病中发挥重要作用。