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.

EBV, memory B cells, multiple sclerosis, natalizumab, plasma cells
dx.doi.org/10.1002/eji.202048739, hdl.handle.net/1765/131937
European Journal of Immunology
Department of Immunology

van Langelaar, J. (Jamie), Wierenga-Wolf, A.F, Samijn, J.P, Luijks, C.J.M. (Caroline J.M.), Siepman, T.A.M, van Doorn, P.A, … van Luijn, M.M. (2020). The association of Epstein-Barr virus infection with CXCR3+ B-cell development in multiple sclerosis: impact of immunotherapies. European Journal of Immunology. doi:10.1002/eji.202048739