Journal
NATURE IMMUNOLOGY
Volume 10, Issue 4, Pages 403-411Publisher
NATURE PORTFOLIO
DOI: 10.1038/ni.1710
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Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NIAID NIH HHS [R37 AI040098, R37 AI040098-13, N01AI40098] Funding Source: Medline
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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 G alpha(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.
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