Circulating human B cells that express surrogate light chains and edited receptors
Circulating human B cells that express surrogate light chains and edited receptors
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DOI：
10.1038/79739
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发表时间：
2000-09-01
影响因子：
30.5
通讯作者：
Nussenzweig, MC
中科院分区：
文献类型：
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作者：
Meffre, E;Davis, E;Nussenzweig, MC
免疫球蛋白基因重组可导致自身反应性抗体的组装。缺失、能量或受体编辑通常会使产生这些自身抗体的B细胞沉默。受体编辑在携带预先重组的自身抗体转基因或基因“敲入”的小鼠B细胞中非常有效。然而，在未经操作的小鼠和人类中，很难识别编辑过受体的细胞。为了鉴定这些细胞，我们从正常人类供者的血液中分离并鉴定了共表达替代轻链和常规轻链(V-preB（+)L(+)）的B细胞。V-preB(+)L(+) B细胞表达RAG mRNA，显示出与抗自身反应性一致的不寻常的重链和轻链抗体库，并显示出受体编辑的证据。这些细胞在类风湿关节炎患者的关节中积累，这与V-preB(+)L(+) B细胞和受体编辑在自身免疫性疾病中的作用一致。
Immunoglobulin gene recombination can result in the assembly of self-reactive antibodies. Deletion, anergy or receptor editing normally silence B cells that produce these autoantibodies. Receptor editing is highly efficient in mouse B cells that carry pre-recombined autoantibody transgenes or gene "knock-ins". However, it has been difficult to identify cells that have edited receptors in unmanipulated mice and humans. To try to identify such cells we isolated and characterized B cells that coexpress surrogate and conventional light chains (V-preB(+)L(+)) from the blood of normal human donors. V-preB(+)L(+) B cells express RAG mRNA, display an unusual heavy and light chain antibody repertoire consistent with antiself reactivity, and show evidence of receptor editing. These cells accumulate in the joints of patients with rheumatoid arthritis, consistent with a role for V-preB(+)L(+) B cells and receptor editing in autoimmune disease.