Shoham Tsipi, Rajapaksa Ranjani, Boucheix Claude, Rubinstein Eric, Poe Jonathan C, Tedder Thomas F, Levy Shoshana
Department of Medicine, Division of Oncology, Stanford University Medical Center, CA 94305-5151, USA.
J Immunol. 2003 Oct 15;171(8):4062-72. doi: 10.4049/jimmunol.171.8.4062.
CD81 is a widely expressed tetraspanin that associates in B cells with CD19 in the CD19-CD21-CD81 signaling complex. CD81 is necessary for normal CD19 expression; cd81(-/-) B cells express lower levels of CD19, especially cd81(-/-) small pre-BII cells, which are almost devoid of surface CD19. The dependence of CD19 expression on CD81 is specific to this particular tetraspanin since cd9(-/-) B cells express normal levels of CD19. Furthermore, expression of human CD81 in mouse cd81(-/-) B cells restored surface CD19 to normal levels. Quantitative analysis of CD19 mRNA demonstrated normal levels, even in cd81(-/-) pre-BII cells. Analysis of CD19 at the protein level identified two CD19 glycoforms in both wild-type and cd81(-/-) B cells. The higher M(r) glycoform is significantly reduced in cd81(-/-) B cells and is endoglycosidase H (endo-H) resistant. In contrast, the low M(r) glycoform is comparably expressed in cd81(-/-) and in wild-type B cells and is endo-H sensitive. Because endo-H sensitivity is tightly correlated with endoplasmic reticulum localization, we suggest that the dependency of CD19 expression on CD81 occurs in a postendoplasmic reticulum compartment where CD81 is necessary for normal trafficking or for surface membrane stability of CD19.
CD81是一种广泛表达的四跨膜蛋白,在B细胞中与CD19 - CD21 - CD81信号复合物中的CD19相关联。CD81是正常CD19表达所必需的;cd81(-/-) B细胞表达较低水平的CD19,尤其是cd81(-/-)小前BII细胞,其几乎没有表面CD19。CD19表达对CD81的依赖性是这种特定四跨膜蛋白所特有的,因为cd9(-/-) B细胞表达正常水平的CD19。此外,在小鼠cd81(-/-) B细胞中表达人CD81可使表面CD19恢复到正常水平。对CD19 mRNA的定量分析表明其水平正常,即使在cd81(-/-)前BII细胞中也是如此。在蛋白质水平对CD19的分析在野生型和cd81(-/-) B细胞中均鉴定出两种CD19糖型。较高分子量的糖型在cd81(-/-) B细胞中显著减少,并且对内切糖苷酶H(endo - H)具有抗性。相反,低分子量的糖型在cd81(-/-)和野生型B细胞中表达相当,并且对endo - H敏感。由于endo - H敏感性与内质网定位密切相关,我们认为CD19表达对CD81的依赖性发生在内质网后区室,其中CD81对于CD19的正常运输或表面膜稳定性是必需的。