Abstract
THE induction of autoantibodies and their possible role in the pathogenesis of autoimmune disease are poorly understood. Involvement of infectious agents has been suspected, but direct evidence is sparse1–4. Whether immunological unresponsiveness to self by antibody-forming ? cells is maintained by clonal abortion5, clonal anergy6–8 or suppression9, or how the scenario of interactions between helper T cells, B cells and antigen-presenting cells10,11–13 is distorted in autoantibody responses, is being analysed and widely debated3,6–8,14–17. To evaluate tolerance of neutralizing B-cell responses12,18 we used transgenic mice expressing the cell membrane associated glycoprotein (G) of vesicular stomatitis virus (VSV) as self-antigen. We show that autoantibodies to VSV-G cannot be induced by VSV-G in adjuvant or by recombinant vaccinia virus expressing VSV-G, but are triggered by infection with wild-type VSV. The data show that helper T-cell tolerance is crucial in maintenance of B-cell non-reactivity2,16,19,20 and that cognate T–B recognition is necessary to break tolerance of self-reactive B cells. These results may help to understand mechanisms of virus-induced autoimmunity.
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Zinkernagel, R., Cooper, S., Chambers, J. et al. Virus-induced autoantibody response to a transgenic viral antigen. Nature 345, 68–71 (1990). https://doi.org/10.1038/345068a0
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DOI: https://doi.org/10.1038/345068a0
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