Coronel-Castello Shila P, Lepennetier Gildas, Diddens Jolien, Friedrich Verena, Pfaller Monika, Hemmer Bernhard, Lehmann-Horn Klaus
Department of Neurology, School of Medicine, Technical University of Munich, Munich, Germany.
Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.
Neurol Ther. 2022 Jun;11(2):905-913. doi: 10.1007/s40120-022-00330-2. Epub 2022 Feb 6.
In spite of antiviral treatment, herpes simplex encephalitis (HSE) remains associated with a poor prognosis and often results in neurological impairment. The B cell response in HSE is poorly understood. The objective of this study was to identify, in a patient with HSE, B cell clones in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs) that expanded between two different time points during the course of infection.
CSF cells and PBMCs were sampled from a HSE patient at two time points 5 days apart. B cells were analyzed using single-cell immune profiling (CSF cells) and conventional deep immune repertoire sequencing (PBMCs).
We identified CSF B cell clones that expanded from time 1 to time 2. Some of these B cell clones could also be found in the peripheral blood. We also report the corresponding B cell receptor (BCR) sequences.
In our patient, HSE resulted in an intrathecal B cell response with expanding CSF clones. We report the B cell receptor sequences of several expanding and dominating clones; these sequences can be used to create recombinant antibodies. Even though the antigen specificity of these expanding clones is unknown, our findings suggest that an adaptive immune response in the central nervous system contributes to repelling herpes simplex virus infection in the brain.
尽管进行了抗病毒治疗，单纯疱疹性脑炎（HSE）的预后仍然较差，且常导致神经功能障碍。人们对HSE中的B细胞反应了解甚少。本研究的目的是在一名HSE患者中，鉴定在感染过程中两个不同时间点之间扩增的脑脊液（CSF）细胞和外周血单核细胞（PBMC）中的B细胞克隆。
从一名HSE患者身上在间隔5天的两个时间点采集CSF细胞和PBMC。使用单细胞免疫分析（CSF细胞）和传统深度免疫组库测序（PBMC）对B细胞进行分析。
我们鉴定出了从时间1到时间2扩增的CSF B细胞克隆。其中一些B细胞克隆在外周血中也能找到。我们还报告了相应的B细胞受体（BCR）序列。
在我们的患者中，HSE导致了鞘内B细胞反应以及CSF克隆的扩增。我们报告了几个扩增和占主导地位的克隆的B细胞受体序列；这些序列可用于制备重组抗体。尽管这些扩增克隆的抗原特异性尚不清楚，但我们的研究结果表明中枢神经系统中的适应性免疫反应有助于抵御大脑中的单纯疱疹病毒感染。
