Intrathecal BCR transcriptome in multiple sclerosis versus other neuroinflammation: Equally diverse and compartmentalized, but more mutated, biased and overlapping with the proteome
Intrathecal BCR transcriptome in multiple sclerosis versus other neuroinflammation: Equally diverse and compartmentalized, but more mutated, biased and overlapping with the proteome
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DOI：
10.1016/j.clim.2015.06.001
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发表时间：
2015-10-01
影响因子：
8.6
通讯作者：
Holmoy, Trygve
中科院分区：
文献类型：
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作者：
Johansen, Jorunn N.;Vartdal, Frode;Holmoy, Trygve
在多发性硬化症（MS）中驱动鞘内IgG合成的机制尚不清楚。我们结合转录免疫球蛋白重链可变区（IGHV）基因的高通量测序和质谱分析，绘制MS患者和其他神经炎性疾病对照的脑脊液（CSF）中IgG产生B细胞的多样性和区室化。在这两组中，少数克隆占主导地位的鞘内IGHV转录组。在大多数MS患者和一些对照组中，显性转录物与CSF IgG相匹配。MS患者CSF中的IGHV转录物经常携带IGHV 4基因，并且与对照相比具有更多的替换突变。在这两组中，显性IGHV转录本在血液中具有相同或相关IGHV转录本的克隆相关B细胞簇内被鉴定。这些发现表明，更明显的亲和力成熟，但同等程度的多样性和划分的鞘内B细胞反应的MS相比，其他神经炎症性疾病。(C)2015 Elsevier Inc. All rights reserved.
The mechanisms driving the intrathecal synthesis of IgG in multiple sclerosis (MS) are unknown. We combined high-throughput sequencing of transcribed immunoglobulin heavy-chain variable (IGHV) genes and mass spectrometry to chart the diversity and compartmentalization of IgG-producing B cells in the cerebrospinal fluid (CSF) of MS patients and controls with other neuroinflammatory diseases. In both groups, a few clones dominated the intrathecal IGHV transcriptome. In most MS patients and some controls, dominant transcripts matched the CSF IgG. The IGHV transcripts in CSF of MS patients frequently carried IGHV4 genes and had more replacement mutations compared to controls. In both groups, dominant IGHV transcripts were identified within clusters of clonally related B cells that had identical or related IGHV transcripts in the blood. These findings suggest more pronounced affinity maturation, but an equal degree of diversity and compartmentalization of the intrathecal B-cell response in MS compared to other neuroinflammatory diseases. (C) 2015 Elsevier Inc. All rights reserved.