Clonal expansion and somatic hypermutation of VH genes of B cells from cerebrospinal fluid in multiple sclerosis
Clonal expansion and somatic hypermutation of VH genes of B cells from cerebrospinal fluid in multiple sclerosis
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DOI：
10.1172/jci3568
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发表时间：
1998-09-01
影响因子：
15.9
通讯作者：
Antel, J
中科院分区：
文献类型：
--
作者：
Qin, YF;Duquette, P;Antel, J
多发性硬化症 (MS) 患者的脑脊液 (CSF) 的特点是免疫球蛋白 (Ig) 浓度升高，电泳分析显示有限的异质性（寡克隆带），CSF Ig 由血清和鞘内产生的成分组成。为了检查鞘内产生抗体的 B 细胞的特性，我们分析了从 12 名 MS 患者和 15 名其他神经系统疾病 (OND) 患者的 CSF 中回收的 B 细胞的 Ig 重链可变 (V-H) 区基因，使用 PCR 技术，我们可以检测所有样本中 Ig V-H 基因的重排。对重排的 VDJ 基因的互补决定区 3 (CDR3) 进行的序列分析显示，12 名 MS 患者中有 10 名出现了一个或多个显性克隆的扩增。在 15 个 OND 中的 3 个中发现了 B 细胞克隆扩增。 MS 患者中克隆扩增的 CSF B 细胞的 V-H 基因的核苷酸序列证明了 V-H IV 家族的优先使用。体细胞突变较多，主要发生在CDR，替换沉默率较高；突变的分布方式表明这些 B 细胞已通过其抗原受体被积极选择。我们的结果表明，在 MS CSF 中，存在大量克隆扩增的 B 细胞，这些细胞具有生发后中心记忆或抗体形成淋巴细胞的特性。
The cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients is characterized by increased concentrations of immunoglobulin (Ig), which on electrophoretic analysis shows restricted heterogeneity (oligoclonal bands), CSF Ig is composed of both serum and intrathecally produced components. To examine the properties of intrathecal antibody-producing B cells, we analyzed Ig heavy-chain variable (V-H) region genes of B cells recovered from the CSF of 12 MS patients and 15 patients with other neurological diseases (OND), Using a PCR technique, we could detect rearrangements of Ig V-H genes in all samples. Sequence analysis of complementarity-determining region 3 (CDR3) of rearranged VDJ genes revealed expansion of a dominant clone or clones in 10 of the 12 MS patients. B cell clonal expansion was identified in 3 of 15 OND. The nucleotide sequences of V-H genes from clonally expanded CSF B cells in MS patients demonstrated the preferential usage of the V-H IV family. There were numerous somatic mutations, mainly in the CDRs, with a high replacement-to-silent ratio; the mutations were distributed in a way suggesting that these B cells had been positively selected through their antigen receptor, Our results demonstrate that in MS CSF, there is a high frequency of clonally expanded B cells that have properties of postgerminal center memory or antibody-forming lymphocytes.