Cervical lymph node B cell subset resists depletion and sustains lytic Epstein Barr-virus signature in patients with multiple sclerosis
- 1Translational Immunology Research Program, University of Helsinki; Helsinki, Finland
Abstract
B cells have arisen as key in multiple sclerosis (MS) pathogenesis by the high efficacy of B cell depleting CD20 monoclonal antibodies and by the identification of Epstein-Barr virus (EBV) as a prerequisite factor. We previously demonstrated an expansion of memory and double negative (DN) B cells in the deep cervical lymph nodes (dcLNs) of newly diagnosed patients with MS (pwMS), with DN B cells showing a molecular signature consistent with lytic EBV infection. Effect of anti-CD20 therapies for pwMS require sustained administration, which led us to hypothesize that incomplete effects on the dcLNs, a natural site for lymphocyte priming towards the central nervous system (CNS), might be sustaining the pathology. Using single-cell transcriptomics and paired sampling, we characterized the effects of anti-CD20 therapies on dcLNs compared to circulation and to other therapies. We observed switched (SM) and unswitched (USM) memory B cells to be depleted uniquely by anti-CD20 in both dcLNs and circulation, whereas DN B cells of the dcLNs were not. Moreover, EBV lytic signature was retained in DN B cells during anti-CD20, and using clonal trajectory we saw that the DN B cells continued to contribute to the plasmablast differentiation within dcLNs. EBV targeting of expanded memory CD8 T cells, as well as CD8 T cell exhaustion, were retained during anti-CD20 therapy within the dcLNs. Our findings suggest a sustained, EBV-driven process in pwMS during anti-CD20 in the CNS-targeting priming dcLNs, with therapeutic implications to be investigated further.
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BibTeX
@misc{babal2026cervical,
title = {{Cervical lymph node B cell subset resists depletion and sustains lytic Epstein Barr-virus signature in patients with multiple sclerosis}},
author = {Y. K. Babal and J. Sarkkinen and E. Ahvenainen and A. Susi and M. Saarela and G. Kurdo and S. M. Laakso},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.25.26366311},
url = {https://www.medrxiv.org/content/10.64898/2026.10.25.26366311v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Cervical lymph node B cell subset resists depletion and sustains lytic Epstein Barr-virus signature in patients with multiple sclerosis
AU - Y. K. Babal
AU - J. Sarkkinen
AU - E. Ahvenainen
AU - A. Susi
AU - M. Saarela
AU - G. Kurdo
AU - S. M. Laakso
PY - 2026
DA - 2026/10/25
PB - medRxiv
DO - 10.64898/2026.10.25.26366311
UR - https://www.medrxiv.org/content/10.64898/2026.10.25.26366311v1
AB - B cells have arisen as key in multiple sclerosis (MS) pathogenesis by the high efficacy of B cell depleting CD20 monoclonal antibodies and by the identification of Epstein-Barr virus (EBV) as a prerequisite factor. We previously demonstrated an expansion of memory and double negative (DN) B cells in the deep cervical lymph nodes (dcLNs) of newly diagnosed patients with MS (pwMS), with DN B cells showing a molecular signature consistent with lytic EBV infection. Effect of anti-CD20 therapies for pwMS require sustained administration, which led us to hypothesize that incomplete effects on the dcLNs, a natural site for lymphocyte priming towards the central nervous system (CNS), might be sustaining the pathology. Using single-cell transcriptomics and paired sampling, we characterized the effects of anti-CD20 therapies on dcLNs compared to circulation and to other therapies. We observed switched (SM) and unswitched (USM) memory B cells to be depleted uniquely by anti-CD20 in both dcLNs and circulation, whereas DN B cells of the dcLNs were not. Moreover, EBV lytic signature was retained in DN B cells during anti-CD20, and using clonal trajectory we saw that the DN B cells continued to contribute to the plasmablast differentiation within dcLNs. EBV targeting of expanded memory CD8 T cells, as well as CD8 T cell exhaustion, were retained during anti-CD20 therapy within the dcLNs. Our findings suggest a sustained, EBV-driven process in pwMS during anti-CD20 in the CNS-targeting priming dcLNs, with therapeutic implications to be investigated further.
ER -