免疫学
脑炎
免疫系统
抗体
自身免疫性脑炎
医学
自身抗体
生物
病毒
作者
Isabelle Wagnon,Pauline Hélie,Isabelle Bardou,Caroline Regnauld,Léonie Lesec,Jérôme Leprince,Mikaël Naveau,Barbara Delaunay,Olivier Toutirais,Brigitte Lemauff,Olivier Etard,Denis Vivien,Véronique Agin,Richard Macrez,Eric Maubert,Fabián Docagne
出处
期刊:Brain
[Oxford University Press]
日期:2020-09-07
卷期号:143 (10): 2957-2972
被引量:38
标识
DOI:10.1093/brain/awaa250
摘要
Abstract Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a neuropsychiatric disease characterized by an antibody-mediated autoimmune response against NMDAR. Recent studies have shown that anti-NMDAR antibodies are involved in the pathophysiology of the disease. However, the upstream immune and inflammatory processes responsible for this pathogenic response are still poorly understood. Here, we immunized mice against the region of NMDA receptor containing the N368/G369 amino acids, previously implicated in a pathogenic response. This paradigm induced encephalopathy characterized by blood–brain barrier opening, periventricular T2-MRI hyperintensities and IgG deposits into the brain parenchyma. Two weeks after immunization, mice developed clinical symptoms reminiscent of encephalitis: anxiety- and depressive-like behaviours, spatial memory impairment (without motor disorders) and increased sensitivity to seizures. This response occurred independently of overt T-cell recruitment. However, it was associated with B220+ (B cell) infiltration towards the ventricles, where they differentiated into CD138+ cells (plasmocytes). Interestingly, these B cells originated from peripheral lymphoid organs (spleen and cervical lymphoid nodes). Finally, blocking the B-cell response using a depleting cocktail of antibodies reduced the severity of symptoms in encephalitis mice. This study demonstrates that the B-cell response can lead to an autoimmune reaction against NMDAR that drives encephalitis-like behavioural impairments. It also provides a relevant platform for dissecting encephalitogenic mechanisms in an animal model, and enables the testing of therapeutic strategies targeting the immune system in anti-NMDAR encephalitis.
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