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首页> 外文期刊>Nature immunology >Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids.
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Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids.

机译:大麻素受体2介导骨髓正弦波中未成熟B细胞的滞留。

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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 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.
机译:在薄壁组织和正弦波中发现了在骨髓中发育的未成熟B细胞。目前尚不清楚控制B细胞在正弦曲线中定位的机制。在这里,我们显示整联蛋白α(4)beta(1)(VLA-4)及其配体VCAM-1是必需的,而趋化因子受体CXCR4对于B细胞的正弦保留是必不可少的。取而代之的是,需要大麻素受体2(CB2)(一种在未成熟B细胞中上调的Galpha(i)蛋白偶联受体)来保持正弦曲线。使用双光子显微镜,我们发现未成熟的B细胞进入正弦波并在正弦波中爬行。这些未成熟的B细胞被CB2拮抗作用所取代。此外,CB2缺陷小鼠外周血和脾脏中免疫球蛋白λ链阳性B细胞的频率较低。我们的发现确定了在骨髓正弦小生境中保留B细胞的独特要求,并暗示了CB2参与B细胞库的产生。

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