Deliberate removal of T cell help improves virus-neutralizing antibody production

Mike Recher; Karl S. Lang; Lukas Hunziker; Stefan Freigang; Bruno Eschli; Nicola L. Harris; Alexander Navarini; Beatrice M. Senn; Katja Fink; Marius Lötscher; Lars Hangartner; Raphaël Zellweger; Martin Hersberger; Alexandre Theocharides; Hans Hengartner; Rolf M. Zinkernagel

doi:10.1038/ni1102

Deliberate removal of T cell help improves virus-neutralizing antibody production

Mike Recher, Karl S. Lang, Lukas Hunziker, Stefan Freigang, Bruno Eschli, Nicola L. Harris, Alexander Navarini, Beatrice M. Senn, Katja Fink, Marius Lötscher, Lars Hangartner, Raphaël Zellweger, Martin Hersberger, Alexandre Theocharides, Hans Hengartner, Rolf M. Zinkernagel

Research output: Contribution to journal › Article › Research › peer-review

78 Citations (Scopus)

Abstract

The B cell response to lymphocytic choriomeningitis virus is characterized by a CD4⁺ T cell-dependent polyclonal hypergammaglobulinemia and delayed formation of virus-specific neutralizing antibodies. Here we provide evidence that, paradoxically, because of polyclonal B cell activation, virus-specific T cell help impairs the induction of neutralizing antibody responses. Experimental reduction in CD4⁺ T cell help in vivo resulted in potent neutralizing antibody responses without impairment of CD8⁺ T cell activity. These unexpected consequences of polyclonal B cell activation may affect vaccine strategies and the treatment of clinically relevant chronic bacterial, parasitic and viral infections in which hypergammaglobulinemia is regularly found.

Original language	English
Pages (from-to)	934-942
Number of pages	9
Journal	Nature Immunology
Volume	5
Issue number	9
DOIs	https://doi.org/10.1038/ni1102
Publication status	Published - 1 Sept 2004
Externally published	Yes

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Recher, M., Lang, K. S., Hunziker, L., Freigang, S., Eschli, B., Harris, N. L., Navarini, A., Senn, B. M., Fink, K., Lötscher, M., Hangartner, L., Zellweger, R., Hersberger, M., Theocharides, A., Hengartner, H., & Zinkernagel, R. M. (2004). Deliberate removal of T cell help improves virus-neutralizing antibody production. Nature Immunology, 5(9), 934-942. https://doi.org/10.1038/ni1102

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title = "Deliberate removal of T cell help improves virus-neutralizing antibody production",

abstract = "The B cell response to lymphocytic choriomeningitis virus is characterized by a CD4+ T cell-dependent polyclonal hypergammaglobulinemia and delayed formation of virus-specific neutralizing antibodies. Here we provide evidence that, paradoxically, because of polyclonal B cell activation, virus-specific T cell help impairs the induction of neutralizing antibody responses. Experimental reduction in CD4+ T cell help in vivo resulted in potent neutralizing antibody responses without impairment of CD8+ T cell activity. These unexpected consequences of polyclonal B cell activation may affect vaccine strategies and the treatment of clinically relevant chronic bacterial, parasitic and viral infections in which hypergammaglobulinemia is regularly found.",

author = "Mike Recher and Lang, {Karl S.} and Lukas Hunziker and Stefan Freigang and Bruno Eschli and Harris, {Nicola L.} and Alexander Navarini and Senn, {Beatrice M.} and Katja Fink and Marius L{\"o}tscher and Lars Hangartner and Rapha{\"e}l Zellweger and Martin Hersberger and Alexandre Theocharides and Hans Hengartner and Zinkernagel, {Rolf M.}",

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Recher, M, Lang, KS, Hunziker, L, Freigang, S, Eschli, B, Harris, NL, Navarini, A, Senn, BM, Fink, K, Lötscher, M, Hangartner, L, Zellweger, R, Hersberger, M, Theocharides, A, Hengartner, H & Zinkernagel, RM 2004, 'Deliberate removal of T cell help improves virus-neutralizing antibody production', Nature Immunology, vol. 5, no. 9, pp. 934-942. https://doi.org/10.1038/ni1102

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AU - Recher, Mike

AU - Lang, Karl S.

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AU - Harris, Nicola L.

AU - Navarini, Alexander

AU - Senn, Beatrice M.

AU - Fink, Katja

AU - Lötscher, Marius

AU - Hangartner, Lars

AU - Zellweger, Raphaël

AU - Hersberger, Martin

AU - Theocharides, Alexandre

AU - Hengartner, Hans

AU - Zinkernagel, Rolf M.

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N2 - The B cell response to lymphocytic choriomeningitis virus is characterized by a CD4+ T cell-dependent polyclonal hypergammaglobulinemia and delayed formation of virus-specific neutralizing antibodies. Here we provide evidence that, paradoxically, because of polyclonal B cell activation, virus-specific T cell help impairs the induction of neutralizing antibody responses. Experimental reduction in CD4+ T cell help in vivo resulted in potent neutralizing antibody responses without impairment of CD8+ T cell activity. These unexpected consequences of polyclonal B cell activation may affect vaccine strategies and the treatment of clinically relevant chronic bacterial, parasitic and viral infections in which hypergammaglobulinemia is regularly found.

AB - The B cell response to lymphocytic choriomeningitis virus is characterized by a CD4+ T cell-dependent polyclonal hypergammaglobulinemia and delayed formation of virus-specific neutralizing antibodies. Here we provide evidence that, paradoxically, because of polyclonal B cell activation, virus-specific T cell help impairs the induction of neutralizing antibody responses. Experimental reduction in CD4+ T cell help in vivo resulted in potent neutralizing antibody responses without impairment of CD8+ T cell activity. These unexpected consequences of polyclonal B cell activation may affect vaccine strategies and the treatment of clinically relevant chronic bacterial, parasitic and viral infections in which hypergammaglobulinemia is regularly found.

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Deliberate removal of T cell help improves virus-neutralizing antibody production

Abstract

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