Grattone M L, Villiers C L, Villiers M B, Drouet C, Marche P N
Laboratoire Immunochimie, CEA-G, DBMS/ICH, INSERM U238, Université Joseph Fourier, Grenoble, France.
Immunology. 1999 Sep;98(1):152-7. doi: 10.1046/j.1365-2567.1999.00839.x.
CR1 and CR2 are expressed as associated proteins on the B-lymphocyte surface. To investigate their respective contributions to the internalization of C3 fragments, transfected murine fibroblasts expressing human CR1, CR2, or both CR1 and CR2 were produced. CR1- and CR1-CR2-expressing cells bound C3b and C3b-dimer whereas CR2- and CR1-CR2-expressing cells bound iC3b and C3de. In all cases, maximum binding was achieved at low ionic strength. CR1-CR2-positive cells internalized two- to threefold more C3b and 1.5-fold more iC3b than CR1- and CR2-single-positive cells, respectively. Internalization of the anti-CR1 antibody J3D3, or C3de was at the same level, in both double-transfected and single-transfected cells. Furthermore, the internalization of C3b dimer by CR1-CR2 cells was impaired in the presence of OKB7, an anti-CR2-blocking antibody, but it was not altered in CR1 cells. Taken together, these findings suggest that CR1 and CR2 collaborate to internalize C3b and iC3b proteins. We suggest that the induction of conformational changes of the ligands enhances their binding to both receptors.
CR1和CR2作为相关蛋白表达于B淋巴细胞表面。为研究它们各自对C3片段内化作用的贡献，制备了表达人CR1、CR2或同时表达CR1和CR2的转染鼠成纤维细胞。表达CR1以及表达CR1 - CR2的细胞结合C3b和C3b二聚体，而表达CR2以及表达CR1 - CR2的细胞结合iC3b和C3de。在所有情况下，低离子强度时可实现最大结合。与仅表达CR1和仅表达CR2的阳性细胞相比，CR1 - CR2阳性细胞内化的C3b多两到三倍，内化的iC3b多1.5倍。在双转染细胞和单转染细胞中，抗CR1抗体J3D3或C3de的内化水平相同。此外，在抗CR2阻断抗体OKB7存在的情况下，CR1 - CR2细胞对C3b二聚体的内化受到损害，但在CR1细胞中未改变。综上所述，这些发现表明CR1和CR2协同作用以使C3b和iC3b蛋白内化。我们认为配体构象变化的诱导增强了它们与两种受体的结合。
