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The association of Epstein‐Barr virus infection with CXCR3(+) B‐cell development in multiple sclerosis: impact of immunotherapies
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 increase...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984177/ https://www.ncbi.nlm.nih.gov/pubmed/33152118 http://dx.doi.org/10.1002/eji.202048739 |
Sumario: | 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. |
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