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Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression
Takashi Matsushita, … , Manabu Fujimoto, Thomas F. Tedder
Takashi Matsushita, … , Manabu Fujimoto, Thomas F. Tedder
Published September 18, 2008
Citation Information: J Clin Invest. 2008;118(10):3420-3430. https://doi.org/10.1172/JCI36030.
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Research Article

Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression

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Abstract

EAE is a mouse T cell–mediated autoimmune disease of the CNS used to model the human condition MS. The contributions of B cells to EAE initiation and progression are unclear. In this study, we have shown that EAE disease initiation and progression are differentially influenced by the depletion of B cells from mice with otherwise intact immune systems. CD20 antibody–mediated B cell depletion before EAE induction substantially exacerbated disease symptoms and increased encephalitogenic T cell influx into the CNS. Increased symptom severity resulted from the depletion of a rare IL-10–producing CD1dhiCD5+ regulatory B cell subset (B10 cells), since the adoptive transfer of splenic B10 cells before EAE induction normalized EAE in B cell–depleted mice. While transfer of regulatory B10 cells was maximally effective during early EAE initiation, they had no obvious role during disease progression. Rather, B cell depletion during EAE disease progression dramatically suppressed symptoms. Specifically, B cells were required for the generation of CD4+ T cells specific for CNS autoantigen and the entry of encephalitogenic T cells into the CNS during disease progression. These results demonstrate reciprocal regulatory roles for B cells during EAE immunopathogenesis. The therapeutic effect of B cell depletion for the treatment of autoimmunity may therefore depend on the relative contributions and the timing of these opposing B cell activities during the course of disease initiation and pathogenesis.

Authors

Takashi Matsushita, Koichi Yanaba, Jean-David Bouaziz, Manabu Fujimoto, Thomas F. Tedder

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Figure 1

B cells regulate EAE severity.

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B cells regulate EAE severity.
B6 mice were treated with CD20 or control...
B6 mice were treated with CD20 or control mAb (250 μg) before or after MOG immunization (days –7, 7, 14, or 21) and scored daily for EAE disease severity. Arrowheads indicate the day of mAb injection. Values represent (mean ± SEM) EAE clinical scores from more than 5 mice in each group, with similar results obtained in 3 independent experiments. Significant differences between CD20 and control mAb–treated groups are indicated; *P < 0.05.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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