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

Immature B-cells developing in the bone marrow (BM) are found in parenchyma and sinusoids. The mechanisms controlling B-cell positioning within sinusoids are not understood. Here we showed that integrin α(4)β(1) and VCAM-1 are required, whereas CXCR4 is dispensable for sinusoidal retention. Instead, cannabinoid receptor 2 (CB2), a Gα(i)-coupled receptor upregulated in immature B-cells, was required for sinusoidal retention. Using two-photon microscopy, we observed immature B-cells entering and crawling within sinusoids; these immature B-cells were displaced by CB2 antagonism. Moreover, CB2-deficient mice contain a reduced frequency of λ(+) B-cells in the peripheral blood and spleen. Our findings identify unique requirements for B-cell retention in the BM sinusoidal niche, and suggest a role for CB2 in B-cell repertoire generation.