Abstract
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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Marrow / immunology
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Bone Marrow / physiology*
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Cell Movement / physiology
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GTP-Binding Protein alpha Subunits / physiology
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Immunoglobulin lambda-Chains / blood
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Immunoglobulin lambda-Chains / immunology
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Integrin alpha4beta1 / immunology
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Integrin alpha4beta1 / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Precursor Cells, B-Lymphoid / cytology
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Precursor Cells, B-Lymphoid / immunology
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Precursor Cells, B-Lymphoid / physiology*
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Receptor, Cannabinoid, CB2 / genetics
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Receptor, Cannabinoid, CB2 / immunology
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Receptor, Cannabinoid, CB2 / physiology*
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Receptors, CXCR4 / immunology
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Receptors, CXCR4 / metabolism
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Spleen / immunology
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Up-Regulation
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Vascular Cell Adhesion Molecule-1 / immunology
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Vascular Cell Adhesion Molecule-1 / physiology
Substances
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CXCR4 protein, mouse
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GTP-Binding Protein alpha Subunits
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Immunoglobulin lambda-Chains
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Integrin alpha4beta1
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Receptor, Cannabinoid, CB2
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Receptors, CXCR4
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Vascular Cell Adhesion Molecule-1