Perivascular clusters of dendritic cells provide critical survival signals to B cells in bone marrow niches.
Beyond its established function in hematopoiesis, the bone marrow hosts mature lymphocytes and acts as a secondary lymphoid organ in the initiation of T cell and B cell responses. Here we report the characterization of bone marrow-resident dendritic cells (bmDCs). Multiphoton imaging showed that bmDCs were organized into perivascular clusters that enveloped blood vessels and were seeded with mature B lymphocytes and T lymphocytes. Conditional ablation of bmDCs in these bone marrow immune niches led to the specific loss of mature B cells, a phenotype that could be reversed by overexpression of the antiapoptotic factor Bcl-2 in B cells. The presence of bmDCs promoted the survival of recirculating B cells in the bone marrow through the production of macrophage migration-inhibitory factor. Thus, bmDCs are critical for the maintenance of recirculating B cells in the bone marrow.
Sapoznikov
Anita
A
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Pewzner-Jung
Yael
Y
Kalchenko
Vyacheslav
V
Krauthgamer
Rita
R
Shachar
Idit
I
Jung
Steffen
S
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001853:Bone Marrow / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D002449:Cell Aggregation / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology*
D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse