Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids

Nat Immunol. 2009 Apr;10(4):403-11. doi: 10.1038/ni.1710. Epub 2009 Mar 1.


Immature B cells developing in the bone marrow are found in the parenchyma and sinusoids. The mechanisms that control the positioning of B cells in the sinusoids are not understood. Here we show that the integrin alpha(4)beta(1) (VLA-4) and its ligand VCAM-1 were required, whereas the chemokine receptor CXCR4 was dispensable, for sinusoidal retention of B cells. Instead, cannabinoid receptor 2 (CB2), a Galpha(i) protein-coupled receptor upregulated in immature B cells, was required for sinusoidal retention. Using two-photon microscopy, we found immature B cells entering and crawling in sinusoids; these immature B cells were displaced by CB2 antagonism. Moreover, CB2-deficient mice had a lower frequency of immunoglobulin lambda-chain-positive B cells in the peripheral blood and spleen. Our findings identify unique requirements for the retention of B cells in the bone marrow sinusoidal niche and suggest involvement of CB2 in the generation of the B cell repertoire.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow / immunology
  • Bone Marrow / physiology*
  • Cell Movement / physiology
  • GTP-Binding Protein alpha Subunits / physiology
  • Immunoglobulin lambda-Chains / blood
  • Immunoglobulin lambda-Chains / immunology
  • Integrin alpha4beta1 / immunology
  • Integrin alpha4beta1 / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Precursor Cells, B-Lymphoid / cytology
  • Precursor Cells, B-Lymphoid / immunology
  • Precursor Cells, B-Lymphoid / physiology*
  • Receptor, Cannabinoid, CB2 / genetics
  • Receptor, Cannabinoid, CB2 / immunology
  • Receptor, Cannabinoid, CB2 / physiology*
  • Receptors, CXCR4 / immunology
  • Receptors, CXCR4 / metabolism
  • Spleen / immunology
  • Up-Regulation
  • Vascular Cell Adhesion Molecule-1 / immunology
  • Vascular Cell Adhesion Molecule-1 / physiology


  • CXCR4 protein, mouse
  • GTP-Binding Protein alpha Subunits
  • Immunoglobulin lambda-Chains
  • Integrin alpha4beta1
  • Receptor, Cannabinoid, CB2
  • Receptors, CXCR4
  • Vascular Cell Adhesion Molecule-1