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Memory B-cell persistence is independent of persisting immunizing antigen

Nature volume 407, pages 636–642 (2000)Cite this article

An Erratum to this article was published on 18 January 2001

Abstract

Immunological memory in the antibody system is generated in T-cell-dependent responses and carried by long-lived memory B cells that recognize antigen by high-affinity antibodies1,2. But it remains controversial1 whether these B cells represent true ‘memory’ cells (that is, their maintenance is independent of the immunizing antigen), or whether they are a product of a chronic immune response driven by the immunizing antigen, which can be retained in the organism for extended time periods on the surface of specialized antigen-presenting cells (follicular dendritic cells)3. Cell transfer experiments provided evidence in favour of a role of the immunizing antigen4,5; however, analysis of memory cells in intact animals, which showed that these cells are mostly resting6 and can persist in the absence of detectable T-cell help7 or follicular dendritic cells8, argued against it. Here we show, by using a genetic switch mediated by Cre recombinase, that memory B cells switching their antibody specificity away from the immunizing antigen are indeed maintained in the animal over long periods of time, similar to cells retaining their original antigen-binding specificity.

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Figure 1: Generation of the VPEinv allele and efficiency of Cre-mediated gene modification in VNP/VPEinv, Mx-cre mice.
Figure 2: Induced change of antigen specificity on mature B cells in vivo .
Figure 3: IFN-induced change of antigen specificity on memory B cells in vivo .
Figure 4: Pattern of somatic mutation in the VPE gene of memory B cells.
Figure 5: Proliferative activity of ‘switched’ PE-binding memory B cells.

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Acknowledgements

We are grateful to B. Hampel, A. Roth and C. Göttlinger for expert technical help, and to T. Kaisho, S. Schwers, L. Pao, A. Ehlich, and R. Küppers for discussion. We also thank S. Casola, P. Oberdoerffer and W. Müller for comments on the manuscript and G. Schmall for help in its preparation. This work was supported by the Volkswagen Foundation, the European Union and the Deutsche Forschungsgemeinschaft. M.M. was recipient of a fellowship from the Alexander von Humboldt Foundation, and K.-P.L. was a fellow of the Human Frontier Science Organization.

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Authors and Affiliations

  1. Institute for Genetics, University of Cologne, Weyertal 121, Cologne, D-50931, Germany

    Mitsuo Maruyama, Kong-Peng Lam & Klaus Rajewsky

  2. Institute of Molecular and Cell Biology, The National University of Singapore, 30 Medical Drive, 117609, Singapore

    Kong-Peng Lam

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  1. Mitsuo Maruyama
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Correspondence to Klaus Rajewsky.

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Maruyama, M., Lam, KP. & Rajewsky, K. Memory B-cell persistence is independent of persisting immunizing antigen . Nature 407, 636–642 (2000). https://doi.org/10.1038/35036600

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