AMPAR immunization induces progressive autoimmune encephalitis with autoreactive B cells in the brain

Overview

Authors: Justus B H Wilke^1,2, George Celis³, Neo Yixuan Peng³, Natalie Sheldon^1,4, Cathy J Spangler¹, Dushyant K Srivastava¹, April Goehring^1,4, Harald Prüss^2,5, Gary Westbrook¹, Lauren B Rodda³, Eric Gouaux^1,4

Vollum Institute, Oregon Health & Science University; Portland, OR, USA
Department of Neurology and Experimental Neurology, Charité – Universitätsmedizin Berlin; Berlin, Germany
Department of Molecular Microbiology and Immunology, Oregon Health & Science University; Portland, OR, USA
Howard Hughes Medical Institute, Oregon Health & Science University; Portland, OR, USA
German Center for Neurodegenerative Diseases (DZNE) Berlin; Berlin, Germany

Journal: bioRxiv : the preprint server for biology, article 2026.05.26.727986

Dates: published online 27 May 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI · PMCID PMC13232205

Status: data only

Categories: mouse (organism), other condition (population), cellular / molecular (subfield)

Citations: 61 references in the paper

Research resources: RRID:SCR_009974

Abstract

AMPA and NMDA receptors are central to synaptic plasticity and cognitive function. In anti-NMDA receptor and anti-AMPA receptor (AMPAR) encephalitis, autoantibodies targeting these receptors disrupt synaptic signaling, leading to severe neuropsychiatric symptoms. However, the cellular autoimmune responses and source of pathogenic autoantibodies during onset and progression of central nervous system (CNS) pathology remain poorly understood. By immunizing mice with intact AMPARs in proteoliposomes, we developed a mouse model of anti-AMPAR encephalitis. Mice developed rapidly progressing neuropsychiatric deficits, autoantibodies targeting the AMPAR amino-terminal domain (ATD) and IgG deposition in the brain, accompanied by reduced AMPAR detection. Throughout disease onset and progression, AMPAR-ATD-specific non-proliferating plasma cells and plasmablasts accumulated in the brain and were predominantly localized in AMPAR-expressing brain parenchyma. In contrast, differentiated AMPAR-ATD specific B cells were far less enriched in peripheral lymphoid tissues. Our results suggest that humoral autoimmune responses directly in the CNS drives disease progression in anti-AMPAR encephalitis.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

zenodo:18151688 — at Zenodo; found in the text, “Footnotes”

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, pages, dates, 11 authors, 61 references, 1 RRID.

Cite

This paper

Wilke, J. B. H., Celis, G., Peng, N. Y., Sheldon, N., Spangler, C. J., Srivastava, D. K., Goehring, A., Prüss, H., Westbrook, G., Rodda, L. B., & Gouaux, E. (2026). AMPAR immunization induces progressive autoimmune encephalitis with autoreactive B cells in the brain. bioRxiv : the preprint server for biology, 2026.05.26.727986.

BibTeX

@article{wilke2026ampar, author = {Wilke, Justus B H and Celis, George and Peng, Neo Yixuan and Sheldon, Natalie and Spangler, Cathy J and Srivastava, Dushyant K and Goehring, April and Prüss, Harald and Westbrook, Gary and Rodda, Lauren B and Gouaux, Eric}, title = {{AMPAR immunization induces progressive autoimmune encephalitis with autoreactive B cells in the brain}}, journal = {bioRxiv : the preprint server for biology}, year = {2026}, month = may, pages = {2026.05.26.727986}, publisher = {Cold Spring Harbor Laboratory Preprints}, pmcid = {PMC13232205} }

RIS

TY - JOUR AU - Wilke, Justus B H AU - Celis, George AU - Peng, Neo Yixuan AU - Sheldon, Natalie AU - Spangler, Cathy J AU - Srivastava, Dushyant K AU - Goehring, April AU - Prüss, Harald AU - Westbrook, Gary AU - Rodda, Lauren B AU - Gouaux, Eric TI - AMPAR immunization induces progressive autoimmune encephalitis with autoreactive B cells in the brain T2 - bioRxiv : the preprint server for biology PY - 2026 DA - 2026/05/27 SP - 2026.05.26.727986 PB - Cold Spring Harbor Laboratory Preprints LA - en ER -

CSL-JSON

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