Hatzfeld A, Fischer E, Levesque J P, Perrin R, Hatzfeld J, Kazatchkine M D
Institut de Cancérologie et d'Immunogenétique, Hôpital Paul Brousse, Villejuif, France.
J Immunol. 1988 Jan 1;140(1):170-5.
The effect of ligand interactions with the C3d/C3dg complement receptor (CR2) on proliferation of human B lymphoblastoid cells was investigated by using cell cultures performed at low density (1 to 1.5 x 10(3) cells/ml) in a serum-free defined medium to which only transferrin had been added. This medium does not allow proliferation of Raji cells which die within 48 hr with formation of polykaryons. Addition of purified human C3 to the cultures resulted in a dose-dependent proliferation of the cells. A steady growth of Raji cells with a doubling time of 36 hr was observed in cultures containing 10 micrograms/ml of C3. A growth rate similar to that observed in the presence of native C3 was found in the presence of equimolar concentrations of purified C3dg but not of C3c. F(ab')2 anti-C3d but not F(ab')2 anti-C3c antibodies inhibited the mitogenic effect of C3. Preincubation of Raji cells with monoclonal antibody OKB7 which directly inhibits the binding of C3dg to CR2, totally suppressed C3-induced growth of the cells. C3 did not enhance growth of the T lymphoma-derived cell line JM and monocytic cell line U937 which do not express CR2. These results provide direct evidence that the interaction between CR2 and C3 fragments stimulates proliferation of human cells of the B lineage. Because CR2 also acts as a receptor for Epstein-Barr virus on B cells, our results may pertain to the B cell mitogenic properties of the virus.
通过在低密度（1至1.5×10³个细胞/毫升）下于仅添加了转铁蛋白的无血清限定培养基中进行细胞培养，研究了配体与C3d/C3dg补体受体（CR2）相互作用对人B淋巴母细胞增殖的影响。这种培养基不允许Raji细胞增殖，Raji细胞在48小时内死亡并形成多核体。向培养物中添加纯化的人C3导致细胞呈剂量依赖性增殖。在含有10微克/毫升C3的培养物中观察到Raji细胞稳定生长，倍增时间为36小时。在等摩尔浓度的纯化C3dg存在下发现生长速率与在天然C3存在下观察到的相似，但在C3c存在下则不然。F(ab')2抗C3d抗体而非F(ab')2抗C3c抗体抑制了C3的促有丝分裂作用。用直接抑制C3dg与CR2结合的单克隆抗体OKB7对Raji细胞进行预孵育，完全抑制了C3诱导的细胞生长。C3并未促进不表达CR2的T淋巴瘤衍生细胞系JM和单核细胞系U937的生长。这些结果提供了直接证据，表明CR2与C3片段之间的相互作用刺激了B谱系人细胞的增殖。由于CR2在B细胞上还作为爱泼斯坦-巴尔病毒的受体，我们的结果可能与该病毒的B细胞促有丝分裂特性有关。
