Modulation and functional involvement of CB2 peripheral cannabinoid receptors during B-cell differentiation
Modulation and functional involvement of CB2 peripheral cannabinoid receptors during B-cell differentiation
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DOI：
10.1182/blood.v92.10.3605.422k05_3605_3615
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发表时间：
1998-11-15
期刊：
影响因子：
20.3
通讯作者：
Casellas, P
中科院分区：
文献类型：
--
作者：
Carayon, P;Marchand, J;Casellas, P
迄今为止，已经鉴定出两种亚型的G蛋白偶联大麻素受体：CB1中枢受体亚型，其主要在脑中表达，以及CB2外周受体亚型，其在免疫系统中显得特别丰富。我们使用抗CB2受体免疫纯化的多克隆抗体研究了白细胞中CB2受体的表达。我们发现外周血和扁桃体B细胞是表达最高量CB 2受体蛋白的白细胞亚群。在扁桃体组织上进行的双色共聚焦显微镜显示CB 2受体在次级卵泡的外套带中的显著表达，而生发中心（GC）被弱染色，这表明在从处女B淋巴细胞到记忆B细胞的分化阶段该受体的调制。事实上，我们在转录和蛋白质水平上都显示了B细胞分化过程中CB2受体表达的明显下调。在GC增殖的中心母细胞中观察到最低的表达。此外，我们研究了大麻素激动剂CP 55，940对CD40介导的处女和GC B细胞亚群增殖的影响。我们发现，CP 55，940增强了两个亚群的增殖，并且这种增强被CB 2受体拮抗剂SR 144528 α阻断，但不被CB 1受体拮抗剂SR 141716 α阻断。最后，我们观察到在CD40介导的活化的前24小时期间，两种B细胞亚群中的CB2受体显著上调。这些数据强烈支持CB2受体参与B细胞分化。(C)1998年，美国血液学会。
Two subtypes of G-protein-coupled cannabinoid receptors hate been identified to date: the CB1 central receptor subtype, which is mainly expressed in the brain, and the CB2 peripheral receptor subtype, which appears particularly abundant in the immune system. We investigated the expression of CB2 receptors in leukocytes using anti-CB2 receptor immunopurified polyclonal antibodies. We showed that peripheral blood and tonsillar B cells were the leukocyte subsets expressing the highest amount of CB2 receptor proteins. Dual-color confocal microscopy performed on tonsillar tissues showed a marked expression of CB2 receptors in mantle zones of secondary follicles, whereas germinal centers (GC) were weakly stained, suggesting a modulation of this receptor during the differentiation stages from virgin B lymphocytes to memory B cells. Indeed, we showed a clear downregulation of CB2 receptor expression during B-cell differentiation both at transcript and protein levels. The lowest expression was observed in GC proliferating centroblasts. Furthermore, we investigated the effect of the cannabinoid agonist CP55,940 on the CD40-mediated proliferation of both virgin and GC B-cell subsets. We found that CP55,940 enhanced the proliferation of both subsets and that this enhancement was blocked by,the CB2 receptor antagonist SR 144528 alpha but not by the CB1 receptor antagonist SR 141716 alpha. Finally, we observed that CB2 receptors were dramatically upregulated in both B-cell subsets during the first 24 hours of CD40-mediated activation. These data strongly support an involvement of CB2 receptors during B-cell differentiation. (C) 1998 by The American Society of Hematology.