Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow.
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.
Institute for Systemic Inflammation Research, University of Lübeck, Ratzeburger Allee 160, Lübeck, Germany.
Oliver
O
Winter
Katrin
K
Moser
Elodie
E
Mohr
Dimitra
D
Zotos
Henriette
H
Kaminski
Martin
M
Szyska
Katrin
K
Roth
David M
DM
Wong
Christof
C
Dame
David M
DM
Tarlinton
Harald
H
Schulze
Ian C M
IC
MacLennan
Rudolf A
RA
Manz
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D002452:Cell Count; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010950:Plasma Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053628:Receptors, Thrombopoietin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055153:Stem Cell Niche / Q000166:cytology / Q000378:metabolism*; D013926:Thrombopoietin / Q000494:pharmacology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism
D015850:Interleukin-6; C481270:Mpl protein, mouse; D053628:Receptors, Thrombopoietin; C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D049452:Green Fluorescent Proteins; D010047:Ovalbumin; D013926:Thrombopoietin