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Eosinophils are required for the maintenance of plasma cells in the bone marrow

Nature Immunology volume 12, pages 151–159 (2011)Cite this article

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Abstract

Plasma cells are of crucial importance for long-term immune protection. It is thought that long-lived plasma cells survive in specialized niches in the bone marrow. Here we demonstrate that bone marrow eosinophils localized together with plasma cells and were the key providers of plasma cell survival factors. In vitro, eosinophils supported the survival of plasma cells by secreting the proliferation-inducing ligand APRIL and interleukin-6 (IL-6). In eosinophil-deficient mice, plasma cell numbers were much lower in the bone marrow both at steady state and after immunization. Reconstitution experiments showed that eosinophils were crucial for the retention of plasma cells in the bone marrow. Moreover, depletion of eosinophils induced apoptosis in long-lived bone marrow plasma cells. Our findings demonstrate that the long-term maintenance of plasma cells in the bone marrow requires eosinophils.

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Figure 1: Bone marrow eosinophils provide plasma cell survival factors.
Figure 2: Eosinophils support the survival of plasma cells through the secretion of soluble factors.
Figure 3: Colocalization of eosinophils and plasma cells in the bone marrow.
Figure 4: Lower expression of APRIL and IL-6 in the bone marrow of eosinophil-deficient mice.
Figure 5: Impaired accumulation of plasma cells in the bone marrow of eosinophil-deficient mice.
Figure 6: Eosinophils are required for the retention of plasma cells in the bone marrow.
Figure 7: The long-term survival of plasma cells is dependent on eosinophils.

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Acknowledgements

We thank N.A. Lee (Mayo Clinic, Scottsdale, Arizona, USA) for MBP-specific antibody; the members of the Deutsches Rheuma-Forschungszentrum, in particular T. Kaiser, for technical support; and R.S. Jack, A. Hegazy and A. Radbruch for critical reading of the manuscript. Supported by Deutsche Forschungsgemeinschaft (BE 1171/2-1 to C.B.; SFB 618 and SFB 650 to M.L.), Bundesministerium für Bildung und Forschung (0315267D to M.L.), the Volkswagen Foundation (Lichtenberg Professorship to M.L.) and the Berlin Senate of Research and Education (to Deutsches Rheuma-Forschungszentrum).

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  1. Toralf Roch

    Present address: Present address: Centre for Biomaterial Development, Helmholtz-Zentrum Geesthacht, Berlin, Germany.,

Authors and Affiliations

  1. Deutsches Rheuma-Forschungszentrum, Institut der Leibniz-Gemeinschaft, Berlin, Germany

    Van Trung Chu, Anja Fröhlich, Gudrun Steinhauser, Tobias Scheel, Toralf Roch, Simon Fillatreau, Max Löhning & Claudia Berek

  2. Department of Rheumatology and Clinical Immunology, Experimental Immunology, Charite-University Medicine, Berlin, Germany

    Anja Fröhlich & Max Löhning

  3. Department of Biochemistry and Molecular Biology, Division of Pulmonary Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA

    James J Lee

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Contributions

V.T.C., C.B. and M.L. designed experiments and analyzed the data; V.T.C. did most of the experiments; A.F. and M.L. analyzed the immune response to LCMV; T.S. analyzed the GC response; J.J.L. contributed the PHIL mouse and eosinophil-specific antibodies; T.R. and G.S. helped with data acquisition; and V.T.C., C.B., M.L., A.F. and S.F. prepared the manuscript.

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Correspondence to Claudia Berek.

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The authors declare no competing financial interests.

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Chu, V., Fröhlich, A., Steinhauser, G. et al. Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nat Immunol 12, 151–159 (2011). https://doi.org/10.1038/ni.1981

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