Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids.
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.
Pereira
João P
JP
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, USA.
An
Jinping
J
Xu
Ying
Y
Huang
Yong
Y
Cyster
Jason G
JG
D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D044385:GTP-Binding Protein alpha Subunits / Q000502:physiology; D007146:Immunoglobulin lambda-Chains / Q000097:blood / Q000276:immunology; D039041:Integrin alpha4beta1 / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology
C514936:CXCR4 protein, mouse; D044385:GTP-Binding Protein alpha Subunits; D007146:Immunoglobulin lambda-Chains; D039041:Integrin alpha4beta1; D043885:Receptor, Cannabinoid, CB2; D019718:Receptors, CXCR4; D019010:Vascular Cell Adhesion Molecule-1