Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow

Author:

Winter Oliver12,Moser Katrin13,Mohr Elodie4,Zotos Dimitra5,Kaminski Henriette3,Szyska Martin13,Roth Katrin3,Wong David M.1,Dame Christof2,Tarlinton David M.5,Schulze Harald6,MacLennan Ian C. M.4,Manz Rudolf A.13

Affiliation:

1. Institute for Systemic Inflammation Research (ISEF), University of Lübeck, Lübeck, Germany;

2. Department of Neonatology, Charité-University Medicine Berlin, Berlin, Germany;

3. German Arthritis Research Center (DRFZ Berlin), Berlin, Germany;

4. MRC Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom;

5. Walter and Eliza Hall Institute of Medical Research, Victoria, Australia; and

6. Laboratory for Pediatric Molecular Biology, Charité-University Medicine Berlin, Berlin, Germany

Abstract

Abstract Long-lived plasma cells in the bone marrow produce memory antibodies that provide immune protection persisting for decades after infection or vaccination but can also contribute to autoimmune and allergic diseases. However, the composition of the microenvironmental niches that are important for the generation and maintenance of these cells is only poorly understood. Here, we demonstrate that, within the bone marrow, plasma cells interact with the platelet precursors (megakaryocytes), which produce the prominent plasma cell survival factors APRIL (a proliferation-inducing ligand) and IL-6 (interleukin-6). Accordingly, reduced numbers of immature and mature plasma cells are found in the bone marrow of mice deficient for the thrombopoietin receptor (c-mpl) that show impaired megakaryopoiesis. After immunization, accumulation of antigen-specific plasma cells in the bone marrow is disturbed in these mice. Vice versa, injection of thrombopoietin allows the accumulation and persistence of a larger number of plasma cells generated in the course of a specific immune response in wild-type mice. These results demonstrate that megakaryocytes constitute an important component of the niche for long-lived plasma cells in the bone marrow.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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