Kaiser E, Förster R, Wolf I, Ebensperger C, Kuehl W M, Lipp M
Institut für Biochemie der Ludwig-Maximilians-Universität München, FRG.
Eur J Immunol. 1993 Oct;23(10):2532-9. doi: 10.1002/eji.1830231023.
The BLR1 gene, isolated initially from Burkitt's lymphoma cells (Eur. J. Immunol. 1992. 22: 2795), encodes a G protein-coupled receptor with significant relationship to receptors for chemokines (IL-8, MIP-1 alpha) and neuropeptides. The murine homologue of human BLR1 was cloned and used to investigate its expression in vivo. blr1-specific transcripts are observed in secondary lymphatic organs and to a lesser extent in brain of adult mice but not in other tissues. RNA in situ hybridization localizes blr1 transcription to primary follicles and to the mantle zone of secondary follicles. SCID mice in which mature B cell development is severely impaired exhibit a strongly reduced level of blr1-specific RNA in the spleen. The analysis of murine lymphoid tumor cell lines representing distinct stages of the B cell lineage reveals elevated expression of blr1 in B cell lymphomas but not in pre-B lymphomas or plasmacytomas. Induction of differentiation of resting B cells by cytokines or mitogens down-regulates expression of blr1. RNA in situ hybridization using brain sections of adult mice detects blr1 transcription in the granule and Purkinje cell layer of the cerebellum. Interestingly, the blr1 gene is also expressed during late embryogenesis in fetal liver and brain. In view of the remarkable expression pattern in the B cell lineage we suggest that murine BLR1 may represent a cytokine/neuropeptide receptor exerting regulatory functions on recirculating mature B lymphocytes.
BLR1基因最初是从伯基特淋巴瘤细胞中分离出来的(《欧洲免疫学杂志》1992年。22: 2795),它编码一种与趋化因子(IL-8、MIP-1α)受体和神经肽受体有显著关系的G蛋白偶联受体。克隆了人类BLR1的小鼠同源物,并用于研究其在体内的表达。在成年小鼠的二级淋巴器官中观察到blr1特异性转录本,在大脑中也有较少程度的表达,但在其他组织中未观察到。RNA原位杂交将blr1转录定位到初级滤泡和二级滤泡的套区。成熟B细胞发育严重受损的SCID小鼠脾脏中blr1特异性RNA水平大幅降低。对代表B细胞谱系不同阶段的小鼠淋巴瘤细胞系的分析显示,blr1在B细胞淋巴瘤中表达升高,但在B前淋巴瘤或浆细胞瘤中不表达。细胞因子或有丝分裂原诱导静息B细胞分化会下调blr1的表达。使用成年小鼠脑切片进行的RNA原位杂交检测到小脑颗粒层和浦肯野细胞层中有blr1转录。有趣的是,blr1基因在胚胎晚期的胎儿肝脏和大脑中也有表达。鉴于其在B细胞谱系中显著的表达模式,我们认为小鼠BLR1可能代表一种对循环成熟B淋巴细胞发挥调节功能的细胞因子/神经肽受体。