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

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.

SUBMITTER: van Langelaar J 

PROVIDER: S-EPMC7984177 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature