Common patterns of B cell perturbation and expanded V4-34 immunoglobulin gene usage in autoimmunity and infection
Common patterns of B cell perturbation and expanded V4-34 immunoglobulin gene usage in autoimmunity and infection
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DOI：
10.1080/08916930310001624656
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发表时间：
2004-02-01
期刊：
影响因子：
3.5
通讯作者：
Potter, KN
中科院分区：
文献类型：
--
作者：
Mockridge, CI;Rahman, A;Potter, KN
系统性红斑狼疮 (SLE) 中淋巴细胞群的特征包括 B 细胞谱紊乱和自身抗体的产生。另一个独特的干扰是 V4-34 编码的血清免疫球蛋白 (Ig) 的过度表达。正常受试者在感染某些疱疹病毒后，V4-34 编码的 Ig 也会出现类似的升高，并且在 Epstein-Barr 病毒 (EBV) 相关的传染性单核细胞增多症 (IM) 中也有发现。为了评估 SLE 和 IM 患者 B 细胞的共同和独特特征，我们比较了 SLE 和 IM 患者的 B 细胞谱和 V4-34 基因参与情况。 IM 患者的 B 细胞谱与 SLE 患者的 B 细胞谱相似，显示幼稚 B 细胞和记忆 B 细胞的不同损失以及浆母细胞/早期浆细胞的维持。来自浆母细胞/早期浆细胞的类转换 V4-34 编码 IgG 在 SLE 和 IM 患者中都很明显，并揭示了寡克隆扩增的共同特征，其中大多数经历了体细胞超突变。有人提出，在健康个体中，V4-34 基因的表达在同种型转换之前被专门审查，作为自身反应性的控制。如果是这样，则在 EBV 感染后绕过审查，然后恢复平衡。 SLE 患者的持续高血清水平可能是由于调节紊乱或内源性病毒的亚临床再激活引起的。
Features of the lymphocyte population in systemic lupus erythematosus (SLE) include a disordered B cell profile and production of autoantibodies. An additional distinctive perturbation is the over-expression of V4-34-encoded serum immunoglobulins (Ig). A similar rise in V4-34-encoded Ig occurs in normal subjects following infection with c ertain herpesviruses, and is found in Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). To assess common and distinctive features of B cells in patients with SLE and IM, we compared the B cell profile and V4-34 gene involvement in patients with SLE and IM. B cell profiles from patients with IM paralleled those of patients with SLE, showing a differential loss of naive and memory B cells and the maintenance of plasmablast/early plasma cells. Class-switched V4-34-encoded IgG from plasmablast/early plasma cells was evident both in patients with SLE and IM and revealed common features of oligoclonal expansions with most having undergone somatic hypermutation. It has been proposed that, in healthy individuals, expression of the V4-34 gene is specifically censored prior to isotype switch as a control on autoreactivity. If so, censoring is bypassed following EBV infection, after which equilibrium is restored. Continuing high serum levels in SLE may arise either by disordered regulation, or by subclinical reactivation of endogenous virus.