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Basophils enhance immunological memory responses

Nature Immunology volume 9, pages 733–742 (2008)Cite this article

Abstract

The cellular basis of immunological memory remains a controversial issue. Here we show that basophils bound large amounts of intact antigens on their surface and were the main source of interleukins 6 and 4 in the spleen and bone marrow after restimulation with a soluble antigen. Depletion of basophils resulted in a much lower humoral memory response and greater susceptibility of immunized mice to sepsis induced by Streptococcus pneumoniae. Adoptive transfer of antigen-reactive basophils significantly increased specific antibody production, and activated basophils, together with CD4+ T cells, profoundly enhanced B cell proliferation and immunoglobulin production. These basophil-dependent effects on B cells required interleukins 6 and 4 and increased the capacity of CD4+ T cells to provide B cell help. Thus, basophils are important contributors to humoral memory immune responses.

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Figure 1: Antigen binding and activation of basophils.
Figure 2: Lower humoral memory response after depletion of basophils.
Figure 3: Fewer antigen-specific B cells and plasma cells after restimulation of mice in the absence of basophils.
Figure 4: Influence of basophils on humoral memory responses during immunization, vaccination and infection.
Figure 5: Enhancement of humoral immune responses by transfer of APC-reactive basophils.
Figure 6: Activated basophils support B cell function.
Figure 7: Basophil-derived IL–6 is required for B cell stimulation.
Figure 8: Influence of CD4+ T cell activation on basophil-induced B cell proliferation and cytokine production.
Figure 9: Basophils induce a 'B helper' phenotype in CD4+ T cells.

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Acknowledgements

We thank K. Schmidbauer, M. Wondrak and N. Göbel for technical assistance, and D. Schlöndorff for critical reading of the manuscript. Supported by the Deutsche Forschungsgemeinschaft (M.M.) and the University Hospital Regensburg.

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Author notes

  1. Cordula Moll & Leoni A Kunz-Schughart

    Present address: Present addresses: Center for Plant Molecular Biology, University of Tübingen, 72076 Tübingen, Germany (C.M.), and OncoRay, Dresden University of Technology, 01307 Dresden, Germany (L.A.K.-S.).,

Authors and Affiliations

  1. Department of Internal Medicine II, University Hospital Regensburg, Regensburg, 93042, Germany

    Andrea Denzel, Manuel Rodriguez Gomez, Cordula Moll, Marianne Niedermeier, Yvonne Talke & Matthias Mack

  2. Department of Pulmonary Medicine, Laboratory for Experimental Lung Research, Hannover School of Medicine, Hannover, 30625, Germany

    Ulrich A Maus, Christine Winter & Regina Maus

  3. Department of Microbiology, University of Alabama at Birmingham, Birmingham, 35294, Alabama, USA

    Susan Hollingshead & David E Briles

  4. Institute of Pathology, University Hospital Regensburg, Regensburg, 93042, Germany

    Leoni A Kunz-Schughart

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Contributions

A.D. contributed to the results in Figures 1,2,3,4,5; U.A.M., C.W., R.M., S.H. and D.E.B. contributed to the results in Figure 4c,d; M.R.G. contributed to the results in Figures 1 and 3; C.M. and L.A.K.-S., contributed to the results in Figures 6,7,8,9; M.N. and Y.T. contributed to the results in Figures 1 and 6,7,8,9; and M.M. contributed to the results in Figures 1,2,3,4,5,6,7,8,9.

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Correspondence to Matthias Mack.

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Denzel, A., Maus, U., Gomez, M. et al. Basophils enhance immunological memory responses. Nat Immunol 9, 733–742 (2008). https://doi.org/10.1038/ni.1621

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