Perivascular clusters of dendritic cells provide critical survival signals to B cells in bone marrow niches

Nat Immunol. 2008 Apr;9(4):388-95. doi: 10.1038/ni1571. Epub 2008 Mar 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Bone Marrow / blood supply
  • Bone Marrow / immunology*
  • Bone Marrow / metabolism
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / metabolism
  • Cell Aggregation / immunology*
  • Cell Survival / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Intramolecular Oxidoreductases / biosynthesis
  • Macrophage Migration-Inhibitory Factors / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Signal Transduction / immunology*

Substances

  • Macrophage Migration-Inhibitory Factors
  • Intramolecular Oxidoreductases
  • Mif protein, mouse