The association of Epstein-Barr virus infection with CXCR3+ B-cell development in multiple sclerosis: impact of immunotherapies

Jamie van Langelaar, Annet F. Wierenga-Wolf, Johnny P.A. Samijn, Caroline J.M. Luijks, Theodora A. Siepman, Pieter A. van Doorn, Andrew Bell, Menno C. van Zelm, Joost Smolders, Marvin M. van Luijn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)
69 Downloads (Pure)

Abstract

Epstein–Barr virus (EBV) infection of B cells is associated with increased multiple sclerosis (MS) susceptibility. Recently, we found that CXCR3-expressing B cells preferentially infiltrate the CNS of MS patients. In chronic virus-infected mice, these types of B cells are sustained and show increased antiviral responsiveness. How EBV persistence in B cells influences their development remains unclear. First, we analyzed ex vivo B-cell subsets from MS patients who received autologous bone marrow transplantation (n = 9), which is often accompanied by EBV reactivation. The frequencies of nonclass-switched and class-switched memory B cells were reduced at 3–7 months, while only class-switched B cells returned back to baseline at 24–36 months posttransplantation. At these time points, EBV DNA load positively correlated to the frequency of CXCR3+, and not CXCR4+ or CXCR5+, class-switched B cells. Second, for CXCR3+ memory B cells trapped within the blood of MS patients treated with natalizumab (anti-VLA-4 antibody n = 15), latent EBV infection corresponded to enhanced in vitro formation of anti-EBNA1 IgG-secreting plasma cells under GC-like conditions. These findings imply that EBV persistence in B cells potentiates brain-homing and antibody-producing CXCR3+ subsets in MS.

Original languageEnglish
Pages (from-to)626-633
Number of pages8
JournalEuropean Journal of Immunology
Volume51
Issue number3
Early online date5 Nov 2020
DOIs
Publication statusPublished - Mar 2021

Bibliographical note

Funding Information:
The authors would like to dedicate this article to the memory of Professor Rogier Q. Hintzen, who passed away on May 15, 2019. We thank Harm de Wit and Peter van Geel for FACS sorting. We thank the patients and healthy controls for donating blood for this study. This work was financially supported by the Dutch MS Research Foundation (14‐875 MS and 15–490d MS). This research was performed within the framework of the Erasmus Postgraduate School Molecular Medicine.

Funding Information:
The authors would like to dedicate this article to the memory of Professor Rogier Q. Hintzen, who passed away on May 15, 2019. We thank Harm de Wit and Peter van Geel for FACS sorting. We thank the patients and healthy controls for donating blood for this study. This work was financially supported by the Dutch MS Research Foundation (14-875 MS and 15?490d MS). This research was performed within the framework of the Erasmus Postgraduate School Molecular Medicine.

Publisher Copyright:
© 2020 The Authors. European Journal of Immunology published by Wiley-VCH GmbH

Fingerprint

Dive into the research topics of 'The association of Epstein-Barr virus infection with CXCR3+ B-cell development in multiple sclerosis: impact of immunotherapies'. Together they form a unique fingerprint.

Cite this