CD19-CAR T-cell therapy resets the EBV+ autoreactive B cell repertoire in autoimmune disease
- 1Stanford University
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.
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BibTeX
@misc{courtney2026cd19car,
title = {{CD19-CAR T-cell therapy resets the EBV+ autoreactive B cell repertoire in autoimmune disease}},
author = {Y. Courtney and M. Pandit and L. S. van Dam and S. Younis and S. Rasouli and M. Zhang and Y. Chaichian and S. Parsafar and T. V. Lanz and E. Arends and C. van Kooten and Y. K. O. Teng and M. Hagen and A. Wirsching and F. Muller and A. Mackensen and A. Bozec and R. Grieshaber-Bouyer and G. Schett and W. H. Robinson},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.24.761515},
url = {https://www.biorxiv.org/content/10.64898/2026.10.24.761515v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - CD19-CAR T-cell therapy resets the EBV+ autoreactive B cell repertoire in autoimmune disease
AU - Y. Courtney
AU - M. Pandit
AU - L. S. van Dam
AU - S. Younis
AU - S. Rasouli
AU - M. Zhang
AU - Y. Chaichian
AU - S. Parsafar
AU - T. V. Lanz
AU - E. Arends
AU - C. van Kooten
AU - Y. K. O. Teng
AU - M. Hagen
AU - A. Wirsching
AU - F. Muller
AU - A. Mackensen
AU - A. Bozec
AU - R. Grieshaber-Bouyer
AU - G. Schett
AU - W. H. Robinson
PY - 2026
DA - 2026/10/24
PB - bioRxiv
DO - 10.64898/2026.10.24.761515
UR - https://www.biorxiv.org/content/10.64898/2026.10.24.761515v1
AB - 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.
ER -