CD19-CAR T-cell therapy resets the EBV+ autoreactive B cell repertoire in autoimmune disease

Epstein-Barr virus (EBV) reprograms autoreactive B cells into activated antigen-presenting cells that drive pathogenic T- and B-cell responses in autoimmune disease. Whether eliminating these cells contributes to durable remission after CD19 chimeric antigen receptor (CAR) T-cell therapy is unknown. Here, using EBV B-cell sequencing (EBV-seq), we profiled EBV+ B cells from patients treated with CD19-CAR T cells (systemic lupus erythematosus, n=6; inflammatory myopathy, n=3; systemic sclerosis, n=3) or rituximab (n=15) and recombinantly expressed their antibodies to define antigen specificity. At baseline, EBV+ B cells were enriched relative to healthy donors, class-switched and hypermutated, expressed the latency III program with heightened antigen-presentation signatures, and encoded autoantibodies. CAR T cells, but not rituximab, depleted EBV+ B cells and shifted the reconstituted repertoire towards IgM+, minimally mutated, largely non-autoreactive cells, consistent with infection of newly generated B cells. After rituximab, EBV+ B cells retained a class-switched, hypermutated and autoreactive with an activated antigen-presenting phenotype. Sustained drug-free remission occurred in 8/12 CAR T-cell-treated versus 0/15 rituximab-treated patients. In vitro, EBV+ B cells resisted anti-CD20 and anti-CD19 antibodies but were killed by CAR T cells and a CD19 T-cell engager. Our findings suggest resetting the EBV+ autoreactive B-cell repertoire contributes to sustained drug-free remission.

Authors

Institutions

Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-11-02
DOI
https://doi.org/10.64898/2026.10.24.761515
Primary Topic
CAR-T cell therapy research
Type
preprint

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
preprint

CD19-CAR T-cell therapy resets the EBV+ autoreactive B cell repertoire in autoimmune disease

Shima Parsafar, Yashaar Chaichian, Andreas Wirsching, Tobias Volker Lanz et al.
5 links
bioRxiv (Cold Spring Harbor Laboratory)
CAR-T cell therapy research
preprint

CD19-CAR T-cell therapy resets the EBV+ autoreactive B cell repertoire in autoimmune disease

Shima Parsafar, Yashaar Chaichian, Andreas Wirsching, Tobias Volker Lanz, William H. Robinson, Laura S. van Dam, Ya’el Courtney, Mahesh Pandit, Eline J. Arends, Melanie Hagen, Mengrui Zhang, Fabian Müller, Dirk Hans Busch, Ricardo Grieshaber‐Bouyer, Cees van Kooten, Aline Bözec, Georg Andreas Schett, Y K Onno Teng, Sajede Rasouli, Shady Younis
preprint en

Abstract

Epstein-Barr virus (EBV) reprograms autoreactive B cells into activated antigen-presenting cells that drive pathogenic T- and B-cell responses in autoimmune disease. Whether eliminating these cells contributes to durable remission after CD19 chimeric antigen receptor (CAR) T-cell therapy is unknown. Here, using EBV B-cell sequencing (EBV-seq), we profiled EBV+ B cells from patients treated with CD19-CAR T cells (systemic lupus erythematosus, n=6; inflammatory myopathy, n=3; systemic sclerosis, n=3) or rituximab (n=15) and recombinantly expressed their antibodies to define antigen specificity. At baseline, EBV+ B cells were enriched relative to healthy donors, class-switched and hypermutated, expressed the latency III program with heightened antigen-presentation signatures, and encoded autoantibodies. CAR T cells, but not rituximab, depleted EBV+ B cells and shifted the reconstituted repertoire towards IgM+, minimally mutated, largely non-autoreactive cells, consistent with infection of newly generated B cells. After rituximab, EBV+ B cells retained a class-switched, hypermutated and autoreactive with an activated antigen-presenting phenotype. Sustained drug-free remission occurred in 8/12 CAR T-cell-treated versus 0/15 rituximab-treated patients. In vitro, EBV+ B cells resisted anti-CD20 and anti-CD19 antibodies but were killed by CAR T cells and a CD19 T-cell engager. Our findings suggest resetting the EBV+ autoreactive B-cell repertoire contributes to sustained drug-free remission.

bioRxiv (Cold Spring Harbor Laboratory)
Friedrich-Alexander-Universität Erlangen-Nürnberg (DE), Leiden University Medical Center (NL), Universitätsklinikum Erlangen (DE), Stanford Medicine (US), Stanford University (US)
Deutsche Forschungsgemeinschaft, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Good health and well-being
CAR-T cell therapy research
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.

Laika access coming soon